Research Programs

Disease-based Programs

Head and Neck Cancer

Clinical Trials

Clinical Trial Information

The following clinical trials are available through the Dana-Farber Cancer Institute Center for Head and Neck Oncology. This list only summarizes patient eligibility criteria. For specific eligibility inquiries or other questions, please contact the Clinical Research Coordinator listed at the end of each trial description.

Many of the studies listed below also include a direct link to the National Cancer Institute's PDQ database for more detailed information.

Investigational Curative Therapy

04-006 A Randomized Phase III Trial Comparing Sequential Therapy with TPF/Chemoradiation (ST) To Cisplatin-Based Chemoradiotherapy with Accelerated Concomitant Boost Radiotherapy (CRT) For Locally Advanced Squamous Cell Cancer of the Head and Neck

Objectives:

To compare the three-year survival achieved by Docetaxel/Cisplatin/5-fluorouracil (TPF) based sequential therapy with platinum based chemoradiotherapy in patients with locally advanced SCCHN; compare the two-year progression free survival achieved by Docetaxel/Cisplatin/5-fluorouracil (TPF) based sequential therapy with platinum based chemoradiotherapy in patients with locally advanced SCCHN; compare survival at five years, progression-free survival at three and five years and the rate of complete response after all therapy; determine and compare site-specific survival within and between each arm; compare functional organ preservation in each arm, the toxicity of each treatment regimen and quality of life; and establish tissue and germ line correlates of response, local regional control, and distant metastases in each arm.

Eligibility:

Histologically or cytologcially proven squamous cell carcinoma of the head and neck. Primary tumor sites eligible: oral cavity, oropharynx, hypopharynx or larynx. At least one uni- or bi-dimensionally measurable lesion. Age ≥18 years. No previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least five years. Any prior treatment with radiotherapy or chemotherapy is an exclusion criterion.

If you have questions or would like further information about this trial, please contact Britta Andreozzi at (617) 582-8039.

06-128 A Phase I Study of Cetuximab/Docetaxel/Cisplatin/5-Fluorouracil (C-TPF) in Patients with Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Objectives:

The primary objective for this clinical trial is to determine the maximum tolerated dose of 5-Fluorouracil in Docetaxel/Cisplatin/5-Fluorouracil (TPF) induction chemotherapy when combined with Cetuximab (C) for locally advanced squamous cell cancer of the head and neck (SCCHN). The secondary objectives are to assess the toxicity of the combination and to determine the response rate (Complete Response and Partial Response) of the combined C-TPF in patients with newly diagnosed SCCHN.

Eligibility:

Histologically or cytologically proven squamous cell carcinoma of the head and neck. Eligible sites: oral cavity, oropharynx, nasopharynx, hypopharynx, larynx or unknown primary site. Stage III or IV disease without evidence of distant metastases. At least one uni- or bi-dimensionally measurable lesion. Age ≥ 18 years. No previous surgery, radiation therapy or chemotherapy for SCCHN (except biopsy or tonsillectomy). No previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years.

If you have questions or would like further information about this trial, please contact Britta Andreozzi at (617) 582-8039.

05-401 A Phase I Study of Panitumumab plus Chemoradiotherapy and Induction Chemotherapy in Patients with Locally Advanced Squamous Cancer of the Head and Neck

Primary objective:

The primary objectives of this study are to identify the maximally tolerated dose (MTD) (or biologically acceptable dose, in the absence of MTD-defining DLT) of paclitaxel given with panitumumab plus carboplatin chemoradiotherapy (Pan-CRT) and to identify the MTD or biologically acceptable dose of TPF, varying the 5-FU dose, given with a fixed dose of panitumumab, prior to concurrent carboplatin, paclitaxel, panitumumab chemoradiotherapy.

Secondary objectives include:

To evaluate the safety and tolerability of the combination of Pan-CRT
To evaluate the safety and tolerability of Pan-TPF
To estimate the overall response rate (ORR) to Pan-TPF
To estimate the ORR of sequential therapy
To estimate the rate of pathologic complete response (pCR) of primary tumor biopsy after Pan-TPF
To estimate 2-year disease free survival (DFS)
To estimate 2-year overall survival (OS)
To evaluate functional outcome at 2 years with respect to speech, swallowing and overall quality of life (QoL)

Eligibility:

To be eligible for the study, patients must fulfill all of the following criteria:

Histologically or cytologically proven squamous cell carcinoma of the head and neck or its variants (such as basaloid squamous cell carcinoma, undifferentiated carcinoma or adenosquamous cell carcinoma).
Primary tumor sites eligible include nasopharynx, oral cavity, oropharynx, hypopharynx, larynx or unknown primary SCCHN.
Stage III or IV disease, without evidence of distant metastasis
No prior chemotherapy, radiotherapy or attempted complete resection of the SCCHN.
≥18 years of age
No history of other malignancy within the previous 5 years, except for non-melanoma skin cancer, carcinoma in situ of the cervix, bladder or head and neck.
Women of childbearing potential (WOCBP) must have a negative pregnancy test within 2 weeks of study entry.
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)
No other serious illnesses or medical conditions
No prior therapy, which affects or targets the ErbB pathway, including any inhibitors of EGFR and ErbB2.

If you have questions or would like further information about this trial, please contact Rafia Khan at (617) 582-8013.

06-283 Randomized Phase II Study Of Docetaxel In Combination With ZACTIMA (ZD6474) In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (SCCHN)

Primary Objectives:

To determine the progression-free survival and the overall survival in both groups of patients
To assess disease control rate and duration of response in both groups of patients
To assess the toxicity of the combination of docetaxel and ZACTIMA. A treatment-limiting toxicity rate is the proportion of subjects discontinuing treatment or study participation due to a safety concern. This rate will be defined as the number of subjects discontinuing from therapy or from the study over the total sample.

Eligibility:

Patients must have:

Histologically/cytologically documented SCCHN, excluding nasopharyngeal carcinoma. Squamous cell carcinomas of unknown primary are allowed. Primary salivary gland tumors and tumors of the nasal cavity and paranasal sinuses are not included.
Be ≥18 years of age.
Evaluable or uni-dimensionally measurable local-regional and/or metastatic disease that is not amenable to primary surgical resection or radiotherapy (according to RECIST)
Locally advanced or metastatic SCCHN. Patients Should have received no more than one trial of palliative chemotherapy after their curative therapy. Curative therapy could have included chemotherapy either in an induction chemotherapy form and/or chemoradiotherapy. Patients must have received a Platinum based regimen prior to enrolling on this protocol and could have received one Biliologocal
A life expectancy of at least 3 months.
An ECOG performance status of 0-2.
Negative pregnancy test for women of childbearing potential
Adequate bone marrow function (i.e., absolute granulocyte count ≥ 1500/mm³ and platelet count ≥ 100,000/mm³).
Be available for follow-up.

Patients must not have had:

Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease ≥2 (see Appendix C) within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age.
Presence of left bundle branch block (LBBB.)
QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG. If a patient has QTc ≥480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the patient to be eligible for the study.)
Any concomitant medication (within 14 days of starting treatment) that may cause QTc prolongation, induce Torsades de Pointes (see Appendix A) or induce CYP3A4 function.
Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
Currently active diarrhea (CTCAE v3 > grade 2) that may affect the ability of the patient to absorb the ZACTIMA or tolerate diarrhea.
Women who are currently pregnant or breast-feeding.
Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in-situ and adequately treated basal cell or squamous cell carcinoma of the skin
Receipt of any investigational agents within 30 days prior to commencing study treatment
Last dose of prior chemotherapy discontinued less than 3 weeks before the start of study therapy
Prior treatment with docetaxel
Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy
Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy
Previous enrollment or randomization of treatment in the present study
Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy

If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.

07-041 A Randomized, Open-Label, Controlled, Phase II Trial of Combination Chemotherapy with or without Panitumumab as First-line Treatment of Subjects with Metastatic or Recurrent Head and Neck Cancer, and Over-over Second-line Panitumumab Monotherapy of Subjects who Fail the Combination Chemotherapy Only Arm

Objectives:

The purpose of this study is to estimate the effect of panitumumab on progression free survival when added to combination chemotherapy in treatment of metastatic or recurrent squamous cell carcinoma of head and neck (SCCHN). The study will also examine response to treatment, and overall survival and safety of the treatment.

Eligibility:

Histologically or cytologically confirmed squamous cell carcinoma of the head and neck or its variants.
Diagnosis of metastatic disease and/or recurrent disease.
No prior systemic treatment for metastatic and/or recurrent SCCHN.
No prior anti-EGFr therapy.
No medical contraindication to therapy.

If you have questions or would like further information about this trial, please contact Rafia Khan at (617) 582-8013.

Chemoprevention

05-361 Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: a Randomized Phase IIb Trial

Objective:

The purpose of this study is to conduct a placebo-controlled, double-blind and randomized 6 month phase IIb cancer control chemoprevention trial of the Bowman-Birk Inhibitor Concentrate (BBIC) in patients with Oral Leukoplakia (OL). This study is being performed to determine whether a product made from soybeans named Bowman-Birk Inhibitor Concentrate (BBIC) affects oral precancerous lesions known as oral leukoplakia (white patch) or erythroplakia (red patch). These types of lesions sometimes, but not always, develop into oral cancer. One of the purposes of this research is to compare the effectiveness of BBIC to an inactive material (called a "placebo") to see if BBIC has any effect on these patches. Another purpose of the study is to see if there are any side effects when taking this medication.

Eligibility:

Patients must have clinically and histologically proven oral leukoplakia and/or erythroplakia and be ≥18 years of age. Women of childbearing potential must not be pregnant and must be willing to use adequate birth control methods. Patients will not be eligible if there has been the use of systemic steroids, or topical oral steroid preparations within three months of the study.

If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.

Trials for patients with recurrent disease

05-379 A Phase II, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Proxinum^® in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck Who Have Received At Least One Prior Anti-cancer Treatment Regimen for Recurrent Disease

Primary objective:

To determine the safety, tolerability, and recommended dose (RD) of intratumorally injected Proxinium^® in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) who have received at least one prior anti-cancer treatment regimen for recurrent disease.

Secondary objectives:

To evaluate principal target tumor and target tumor response rates following intratumoral injection of Proxinium^®
To determine the time to progression of the principal target tumor following intratumoral injection of Proxinium^®
To determine overall survival time associated with intratumorally injected Proxinium^®
To determine progression-free survival as assessed by evaluation of the principal target tumor following intratumoral injection of Proxinium^®
To confirm the pharmacokinetic (PK) profile of intratumorally injected Proxinium^®
To assess immunogenicity of intratumorally injected Proxinium^®

Eligibility:

The patient must have histologically confirmed SCCHN.
The patient must have immunohistochemically confirmed epithelial cell adhesion molecule (Ep-CAM)-positive SCCHN.
The patient must have received therapy for their primary disease (ie, SCCHN) consisting of radiotherapy with or without surgery and with or without chemotherapy.
Patients must have documented recurrent disease following therapy for their primary disease.
Patients must have progressed on or after receiving at least 1 prior anti-cancer treatment regimen containing 1 or more anti-cancer agents (eg, chemotherapy, biologic therapy, or photodynamic therapy for their recurrent disease.

If you have questions or would like further information about this trial, please contact Sonia Kim at (617) 632-5587.

04-358 A Phase II Study of Single-Agent Depsipeptide in Patients with Unresectable or Metastatic Squamous Cell Carcinoma of the Head and Neck

Primary objective:

The primary objective of this study is to evaluate the rate of disease control (i.e., achievement of complete response, partial response, or stable disease) of the single agent depsipeptide in patients with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck.

Secondary objective:

The secondary objective of this study is to evaluate the duration of response, time to progression, and overall survival for patients with incurable head and neck cancer treated with depsipeptide.

Eligibility:

To be eligible for the study, patients must fulfill all of the following criteria:

Histologically or cytologically confirmed squamous cell cancer of the head and neck that must be incurable with surgery or radiation therapy.
No nasopharyngeal primaries
The tumor should preferably be present at the primary site, and it must be accessible for biopsy
Patients may have received up to one prior systemic chemotherapy regimen for unresectable, recurrent or metastatic disease. Chemotherapy must have been completed at least 4 weeks prior to entry into the study. Patients treated previously with mitomycin C and nitrosoureas should have a therapy-free interval of at least 6 weeks duration prior to study entry. If patients have received doxorubicin in the past, their cumulative dose of doxorubicin should not be more than 450 mg/m². Palliative radiation therapy is allowed but must have been completed at least 4 weeks prior to study entry. However, any primary, curative intent radiotherapy with or without chemotherapy must have been administered at least 6 months prior to study entry; in this case, patients may not have any prior chemotherapy for their recurrent disease. If the only site of measurable disease is a previously irradiated area, the patient must have documented progressive disease or biopsy-proven residual carcinoma. Persistent disease after radiotherapy must be biopsy-proven at least 8 weeks after the completion of radiotherapy.
No prior biologic therapy
No prior therapy with depsipeptide or other investigational agents/ drugs known to have histone deacetylase inhibitor activity such as sodium valproate.
≥18 years of age.
Life expectancy of greater than 3 months.
No significant cardiac disease including congestive heart failure or history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias, history of cardiac hypertrophy or poorly controlled angina.
No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix. Patients with prior malignancies who have been disease-free for more than 2 years are eligible.
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
A negative serum pregnancy test is required less than 2 weeks of randomization for women who are still menstruating.
Patients may not be co-medicated with an agent that causes QTc prolongation or hydrochlorothiazide (HCTZ)
No other serious uncontrolled illnesses or medical conditions
No patients with immune deficiency that are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with depsipeptide.

If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.

06-111 Randomized Phase II Study of Bevacizumab/Tarceva^® and Tarceva^®/Sulindac in Squamous Cell Carcinoma of the Head and Neck

Primary Objective:

The primary objective of this randomized Phase II study is to evaluate the efficacy of erlotinib (also called Tarceva^®) plus bevacizumab (also called Avastin^®) (Arm A) or erlotinib (Tarceva^®) plus sulindac (Arm B) in subjects with incurable recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN), as measured by progression-free survival (PFS).

Secondary Objective:

Secondary objectives include: evaluation of the overall response rate (ORR) of erlotinib (Tarceva^®) plus bevacizumab (Avastin^®) or sulindac in subjects with incurable SCCHN; evaluation of the duration of overall survival and objective response with erlotinib (Tarceva^®) plus bevacizumab (Avastin^®) or sulindac in this patient population (rates of PFS at 4 months and 1 year will also be determined); evaluation of the safety and side effects of erlotinib (Tarceva^®) plus bevacizumab (Avastin^®) or sulindac in subjects with incurable SCCHN; and to bank pre- and post-treatment tissue specimens in a subset of subjects for exploration molecular markers associated with response.

Eligibility:

Subjects must be 18 years of age or older with histologically/ cytologically documented squamous cell carcinoma of the head and neck. Subjects must have evaluable locoregional and/or metastatic disease that is not appropriate for treatment by primary surgical resection or radiotherapy. Subjects must have failed to respond to or relapsed from at least once prior chemotherapy or chemoradiotherapy. Subjects will be excluded from this study if they have had: more than one prior systemic therapy for recurrent and/or metastatic disease, any other malignancy within 5 years (except non-melanomatous skin cancer, or carcinoma in situ of the cervix, bladder or head and neck), concurrent anticancer therapy (other than that of this study), treatment with any anticancer drug within 28 days of beginning this study, radiotherapy within 28 days of beginning this study, any prior therapy which targets the ErbB and/or VEGF pathways (including oral kinase inhibitors and antibody therapy), concurrent therapy with any NSAID (except aspirin at a dose of no more than 81 mg per day), known hypersensitivity characterized by acute bronchospasm, urticaria and/or rhinitis to NSAIDs (including aspirin). Subjects will also be excluded form this study if they have other serious illnesses or medical conditions, a tumor that encases the carotid artery (or other major vessel that in the opinion of investigators is at risk for tumor-related hemorrhage), or have the presence of central nervous system or brain metastases.

If you have questions or would like further information about this trial, please contact Rafia Khan at (617)582-8013.

06-179 A Pilot Feasibility Study of Epstein-Barr Virus-Specific Immunotherapy for Nasopharyngeal Carcinoma

Objectives:

The primary objective for this Pilot study is to determine the feasibility and safety of generating and administering at least 2 infusions of Epstein-Barr Virus (EBV)-specific adoptive T cells in subjects with incurable locoregional relapsed and/or distant metastatic EBV-associated nasopharyngeal carcinoma (NPC). The data collected from this Pilot study will provide the basis for a Phase II study to establish the clinical efficacy of EBV-specific adoptive immunotherapy for the treatment of NPC. Basic science studies aimed at understanding the mechanisms underlying effective EBV-specific immunotherapy will also be initiated in this Pilot study and should allow more advanced studies of specific EBV-associated immune factors in a future Phase II clinical trial.

Eligibility:

Histologically or cytologically proven NPC of any WHO grade associated with EBV as documented by the presence of EBER by immunohistochemistry in the tumor. Incurable NPC as defined by relapsed or progressive disease at the primary site and/or regional lymph nodes after initial treatment with no potential curative option OR NPC with distant metastasis. Age > 18 years and ECOG Performance Status ≤ 1. No prior radiotherapy for primary NPC within 8 weeks of enrollment or chemotherapy for NPC within 2 weeks of enrollment. No other cancer within 5 years, with the exception of carcinoma in situ of the cervix or bladder, or non-melanoma skin cancer. No uncontrolled central nervous system metastases. Certain significant medical conditions may be exclusionary.

If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.

Thyroid Cancer

06-188 A Phase II, Open-Label Study to Assess the Efficacy and Tolerability of ZD6474 (ZACTIMA) 100 mg Monotherapy In Subjects with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer.

Objective:

The primary objective of this study is to determine the objective response rate in subjects treated with ZD6474 monotherapy. Secondary objectives are to determine the safety and tolerability of ZD6474 treatment in this patient population, to determine the progression free survival of hereditary MTC in subjects following ZD6474 100 mg therapy, as well as the disease control rate, duration of objective response, and duration of disease control with ZD6474. Secondary objectives also include assessment of performance status as well as bowel frequency changes during therapy, in addition to an assessment of the effect of ZD6474 on calcitonin and CEA levels, and to characterize the population pharmacokinetic of ZD6474 in subjects with hereditary MTC.

Eligibility:

Potiential subjects must be over 18 years of age, WHO Performance status of 0-2, at least one measureable lesion greater than 1 cm on spiral CT, and women of childbearing potential must have a negative pregnancy test. Only subjects with the hereditary form of medullary thyroid cancer will be eligible for entry into this trial. Subjects must not have brain metastases or spinal cord compression, unless irradiated at least four weeks before the first dose and stable without steroid treatment for greater than one week. Subjects must have had their last surgical procedure, dose of chemotherapy or radiation, at least four weeks before starting study. Subjects must not have significant cardiac issues that put them at risk of ventricular arrhythmia, or asymptomatic sustained ventricular tachycradia, or congenital long QT syndrome, or first degree relative with unexplained death under 40 years of age. Subjects cannot have a left bundle branch block, uncontrolled hypertension, previous malignancies at other sites within five years of study start, with the exception of in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin.

Compensation:

There may be funds available to aid any patient who wishes to participate, but will require a large travel expenditure. Details regarding travel reimbursement may be discussed further with the study staff.

If you have questions or would like further information about this trial, please contact Jeff Miller at (617) 632-2503.

06-252 A Phase II, Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study to Assess the Efficacy of ZD6474 (ZACTIMA) versus Placebo in Subjects with Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer

Objective:

This will be a Phase II, randomized study to establish the effect of once-daily oral doses of ZD6474 300mg vs placebo in subjects with locally advanced or metastatic hereditary or sporadic medullary thyroid cancer in whom no standard therapeutic option is available.

It will be conducted in a minimum of 232 subjects in approximately 58 countries. The subjects may continue with ZD6474 as long as they are receiving clinical benefit or until they are given another anti-cancer therapy.

Eligibility:

To participate in study you must:

Be 18 years or older ; Have confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic MTC ; Have a measurable tumor; Be able to swallow medication

You are not able to participate if you have:

Had major surgery within 4 weeks before randomization; Received the last dose of prior chemotherapy less than 4 weeks prior to randomization; Had radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy); Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days; Significant cardiac events; Had previous ZD6474 treatment

If you have questions or would like further information about this trial, please contact Jeff Miller at (617) 632-2503.

06-321 A Pivotal Phase 2 Study of the Anti-Angiogenesis Agent AG-013736 in Patients with ¹³¹I-refractory metastatic or Unresectable locally-advanced papillary, follicular, or Hurthle-cell thyroid cancer who are also refractory to, or intolerant of, or have clinical contraindication to, doxorubicin treatment

Primary Objective:

The primary objective of this study is to determine the objective response rate (ORR) of patients with ¹³¹I-refractory metastatic or unresectable locally-advanced papillary, follicular, or Hurthle-cell thyroid cancer who are also refractory to, or intolerant of, or have clinical contraindication to, doxorubicin treatment.

Inclusion Criteria:

Histologically documented, ¹³¹I-refractory metastatic or unresectable locally-advanced thyroid cancer of papillary, follicular or Hurthle cell histology.
- Failure of doxorubicin (either as a single agent or in combination with other agents) to control the disease, documented with radiographic evidence of disease progression as defined by RECIST criteria and documented with 2 sets of CT/MRI scans or 2 sets of chest x-rays during doxorubicin therapy or within 6 months after the last dose of doxorubicin (scans or chest x-rays must be received and verified by imaging core laboratory before patient can receive treatment);
- Intolerance of doxorubicin therapy, defined as occurrence of life-threatening or grade 4 toxicity attributable to previous therapy with doxorubicin (a maximum of 10 patients will be eligible under this criteria);
- Doxorubicin therapy is clinically contraindicated, defined as patients who have received a cumulative doxorubicin dose of >450 mg/m² during previous therapy.
If a patient has only locally-advanced cancer without distant metastasis, in addition to satisfying the above inclusion criteria, the disease must also be unresectable (eg, tumor involving vital structure, history of previous surgery in the same area, or concurrent severe medical condition that prevents surgery) AND must be refractory to external beam radiotherapy.
At least 1 measurable target lesion, as defined by RECIST. If the only measurable target lesion is located in an externally irradiated field, this lesion may be used as measurable disease only if the lesion diameter has grown by≥20 % since completion of the prior external irradiation or if the lesion is a new lesion, assuming all other criteria are met (CT/MRI scans must be received and verified by imaging core laboratory before patient can receive treatment). Baseline scans must be received by the imaging core laboratory before the patient can receive treatment with AG-013736.
Adequate hepatic, and renal function documented within 14 days prior to treatment as documented by:
- AST and ALT ≤2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT ≤5.0 x ULN
- total bilirubin ≤1.5 x ULN
- serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min
- urinary protein <2+ by urine dipstick. If dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours
Age ≥18 years.
ECOG performance status of 0 or 1 (see Appendix D)
No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140, and the baseline diastolic blood pressure readings must be ≤90. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to treatment.

Exclusion Criteria:

Central lung lesions involving major blood vessels (arteries or veins). (Central lesions that maintain the structural integrity of vessels have the potential to bleed if the tumor lesion undergoes necrosis. MRI or CT angiography should be used in any case where there is any question as to whether blood vessels are involved.)
Thyroid lymphoma or anaplastic or medullary histology
Bleeding from lung (as evidenced by hemoptysis) > 1/2 tsp of bright red blood per day within past 1 week
Gastrointestinal abnormalities including:
- inability to take oral medication
- requirement for intravenous alimentation
- prior surgical procedures affecting absorption including gastric resection
- treatment for active peptic ulcer disease in the past 6 months
- active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
- malabsorption syndromes.
Previous treatment with anti-angiogenesis agents including thalidomide, Sutent (SU-011248), AMG 706, sorafenib, and bevacizumab.
Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine).
Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John's wort).
Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism.
History of a malignancy (other than thyroid cancer) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years
Major surgical procedure within 4 weeks of treatment.
Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
Patients (male and female) having procreative potential who are not using adequate contraception or practicing abstinence.
Women who are pregnant or breast-feeding.

If you have questions or would like further information about this trial, please contact Rafia Khan at (617) 582-8013.

Phaseone

Phase I Trials

06-416 An Open-Label, Randomized, Phase 1b Study Evaluating the Effect of Different Doses of AMG 706 on the Gallbladder in Subjects with Advanced Solid Tumors

Primary Objective:

The primary objective of this study is to evaluate the effect of AMG 706 monotherapy administered according to three different dosing schemes on the change in size (volume) and function (eject fraction) of the gallbladder.

Secondary Objective(s):

To evaluate overall changes in selected other gallbladder characteristics (e.g. length, width, height, area, wall thickness, and ductal dilation/size,
To evaluate reversibility of the size (volume) and function (eject fraction) of the gallbladder following withdrawl of AMG 706,
To evaluate the pharmacokinetics of AMG 706 at various dosing schemes in all three treatment arms,
To evaluate the safety and tolerability of AMG 706 in all three treatment arms, and
To evaluate objective response rates in subjects with advanced solid tumors receiving AMG 706 monotherapy.

Eligibility:

Key Inclusion Criteria:

Histology confirmed advanced metastatic solid tumor
Ineligible to receive or progressed on standard of care therapies
Measurable or non-measurable disease per modified RECIST (Response Evaluation Criteria in Solid Tumor)
Gallbladder must be in situ on screening ultrasound
ECOG Performance Status of 0 to 2
Life expectancy of > 6 months as determined by the investigator
Adequate organ and hematological function as evidenced by laboratory studies prior to randomization
Men and women > 18 years old

Key Exclusion Criteria:

Uncontrolled central nervous system metastases
Known history of prior episodes of cholecystitis, prior biliary procedure (ie, ERCP, biliary stent), or prior or on-going biliary disease
Radiation therapy within 14 days prior to randomization
Peripheral neuropathy > grade 1 per Common Terminology Criteria for Adverse Events (CTCAE version 3.0)
Currently or previous treated with AMG 706, or other small molecule inhibitors of VEGF including, but not limited to, SU11248 (sunitinib), PTK787 (vatalanib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib), ZD6474 (vandetanib)
Subjects who have been previously treated with bevacizumab will be permitted if at least 6 weeks (42 days) have elapsed from the last dose of bevacizumab to the date of randomization
Any anticoagulation therapy within 7 days prior to randomization. The use of low-dose warfarin [<2 mg daily] or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis is allowed
Less than 30 days since ending an investigational device or drug trial from randomization, or currently receiving other investigational treatments
History of arterial or venous thrombosis within 1 year prior to randomization
History of bleeding diathesis or bleeding within 14 days of randomization
Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, grade 2 or greater peripheral vascular disease, arrythmias not controlled by outpatient medication, or unstable angina within 1 year prior to randomization
Uncontrolled hypertension as defined by resting blood pressure > 150/90 mm Hg. Anti-hypertensive medications are allowed if the medications are allowed if the subject is stable at the time of randomization
Surgery:
- Major surgical procedure within 4 weeks (28 days) prior to randomization
- Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of randomization
- Planned elective surgery while on study
Non-healing or open wound, ulcer, or fracture
Known ongoing or active infection
Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
Known chronic hepatitis
Known history of allergic reaction or hypersensitivity to AMG 706 or any of its components
Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding

For further information on this study, please contact the research coordinator for this trial, Jayme Flynn at (617) 632-5260.

Phase I/II Trial of Abraxane in Combination with Carboplatin, Erbitux and Intensity Modulated Radiation Therapy (IMRT) for Treatment of Locally Advanced Squamous Cancer of the Head and Neck

Objectives: The primary objective for the phase I portion of this clinical trial is to identify the maximally tolerated dose of Abraxane given with carboplatin and Erbitux plus concurrent IMRT (ACE-RT) for locally advanced SCCHN. I In the phase II portion of the study, the objective is evaluate the efficacy of this regimen by evaluating 2-year disease-free survival. The secondary objectives are to evaluate the safety and tolerability of the combination of Abraxane, carboplatin and Erbitux, to estimate the overall response rate to ACE-RT, to estimate 2-year overall survival, and to evaluate functional outcome at 2 years with respect to speech, swallowing and overall quality of life .

Eligibility: Histologically or cytologically proven squamous cell carcinoma of the head and neck.

Eligible sites: oral cavity, oropharynx, nasopharynx, hypopharynx, larynx or unknown primary site. Stage III or IV disease without evidence of distant metastases. At least one uni- or bi-dimensionally measurable lesion. Age > 18 years. No previous surgery, radiation therapy or chemotherapy for SCCHN (except biopsy or tonsillectomy). No previous or current malignancies at other sites, with the exception of non-melanoma skin cancer, carcinoma in situ of the cervix, bladder or head and neck. No prior therapeutic radiation to the head and neck. No prior therapy which targets the EGFR pathway.

If you have questions or would like further information about this trial, please contact Jeff Miller at (617) 632-2503

Non-protocol

Non-protocol treatments

Salivary gland cancer/adenoid cystic carcinoma:

Second line chemotherapy with Cytoxan, Adriamycin and Oxaliplatin for patients who have not had prior exposure to these three drugs and who have progressed on other chemotherapy for metastatic or recurrent disease. Cycles are every 3-4 weeks.

Recurrent or metastatic nasopharynx cancer:

First line salvage for possible cure. ABIM (Adriamycin, Bleomycin, Ifosfamide and Mesna). Patients with metastatic disease, or locally recurrent disease for which further radiation is not recommended, no prior systemic chemotherapy for recurrence, no radiation to sites outside the head and neck. This therapy requires hospitalization for 4 days, a venous access device and careful monitoring. Cycles are every three to four weeks. Radiotherapy is planned for limited stage recurrences.

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Research Programs Disease-based Programs Head and Neck Cancer Clinical Trials Clinical Trial Information The following clinical trials are available through the Dana-Farber Cancer Institute Center for Head and Neck Oncology. This list only summarizes patient eligibility criteria. For specific eligibility inquiries or other questions, please contact the Clinical Research Coordinator listed at the end of each trial description. Investigational Curative Therapy Chemoprevention Recurrent Disease Thyroid Cancer Phase I Trials Non-Protocol Treatments Many of the studies listed below also include a direct link to the National Cancer Institute's PDQ database for more detailed information. Investigational Curative Therapy 04-006 A Randomized Phase III Trial Comparing Sequential Therapy with TPF/Chemoradiation (ST) To Cisplatin-Based Chemoradiotherapy with Accelerated Concomitant Boost Radiotherapy (CRT) For Locally Advanced Squamous Cell Cancer of the Head and Neck Objectives: To compare the three-year survival achieved by Docetaxel/Cisplatin/5-fluorouracil (TPF) based sequential therapy with platinum based chemoradiotherapy in patients with locally advanced SCCHN; compare the two-year progression free survival achieved by Docetaxel/Cisplatin/5-fluorouracil (TPF) based sequential therapy with platinum based chemoradiotherapy in patients with locally advanced SCCHN; compare survival at five years, progression-free survival at three and five years and the rate of complete response after all therapy; determine and compare site-specific survival within and between each arm; compare functional organ preservation in each arm, the toxicity of each treatment regimen and quality of life; and establish tissue and germ line correlates of response, local regional control, and distant metastases in each arm. Eligibility: Histologically or cytologcially proven squamous cell carcinoma of the head and neck. Primary tumor sites eligible: oral cavity, oropharynx, hypopharynx or larynx. At least one uni- or bi-dimensionally measurable lesion. Age ≥18 years. No previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least five years. Any prior treatment with radiotherapy or chemotherapy is an exclusion criterion. *If you have questions or would like further information about this trial, please contact Britta Andreozzi at (617) 582-8039.* 06-128 A Phase I Study of Cetuximab/Docetaxel/Cisplatin/5-Fluorouracil (C-TPF) in Patients with Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck Objectives: The primary objective for this clinical trial is to determine the maximum tolerated dose of 5-Fluorouracil in Docetaxel/Cisplatin/5-Fluorouracil (TPF) induction chemotherapy when combined with Cetuximab (C) for locally advanced squamous cell cancer of the head and neck (SCCHN). The secondary objectives are to assess the toxicity of the combination and to determine the response rate (Complete Response and Partial Response) of the combined C-TPF in patients with newly diagnosed SCCHN. Eligibility: Histologically or cytologically proven squamous cell carcinoma of the head and neck. Eligible sites: oral cavity, oropharynx, nasopharynx, hypopharynx, larynx or unknown primary site. Stage III or IV disease without evidence of distant metastases. At least one uni- or bi-dimensionally measurable lesion. Age ≥ 18 years. No previous surgery, radiation therapy or chemotherapy for SCCHN (except biopsy or tonsillectomy). No previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years. *If you have questions or would like further information about this trial, please contact Britta Andreozzi at (617) 582-8039.* 05-401 A Phase I Study of Panitumumab plus Chemoradiotherapy and Induction Chemotherapy in Patients with Locally Advanced Squamous Cancer of the Head and Neck Primary objective: The primary objectives of this study are to identify the maximally tolerated dose (MTD) (or biologically acceptable dose, in the absence of MTD-defining DLT) of paclitaxel given with panitumumab plus carboplatin chemoradiotherapy (Pan-CRT) and to identify the MTD or biologically acceptable dose of TPF, varying the 5-FU dose, given with a fixed dose of panitumumab, prior to concurrent carboplatin, paclitaxel, panitumumab chemoradiotherapy. Secondary objectives include: To evaluate the safety and tolerability of the combination of Pan-CRT To evaluate the safety and tolerability of Pan-TPF To estimate the overall response rate (ORR) to Pan-TPF To estimate the ORR of sequential therapy To estimate the rate of pathologic complete response (pCR) of primary tumor biopsy after Pan-TPF To estimate 2-year disease free survival (DFS) To estimate 2-year overall survival (OS) To evaluate functional outcome at 2 years with respect to speech, swallowing and overall quality of life (QoL) Eligibility: To be eligible for the study, patients must fulfill all of the following criteria: Histologically or cytologically proven squamous cell carcinoma of the head and neck or its variants (such as basaloid squamous cell carcinoma, undifferentiated carcinoma or adenosquamous cell carcinoma). Primary tumor sites eligible include nasopharynx, oral cavity, oropharynx, hypopharynx, larynx or unknown primary SCCHN. Stage III or IV disease, without evidence of distant metastasis No prior chemotherapy, radiotherapy or attempted complete resection of the SCCHN. ≥18 years of age No history of other malignancy within the previous 5 years, except for non-melanoma skin cancer, carcinoma in situ of the cervix, bladder or head and neck. Women of childbearing potential (WOCBP) must have a negative pregnancy test within 2 weeks of study entry. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) No other serious illnesses or medical conditions No prior therapy, which affects or targets the ErbB pathway, including any inhibitors of EGFR and ErbB2. *If you have questions or would like further information about this trial, please contact Rafia Khan at (617) 582-8013.* 06-283 Randomized Phase II Study Of Docetaxel In Combination With ZACTIMA (ZD6474) In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (SCCHN) Primary Objectives: To determine the progression-free survival and the overall survival in both groups of patients To assess disease control rate and duration of response in both groups of patients To assess the toxicity of the combination of docetaxel and ZACTIMA. A treatment-limiting toxicity rate is the proportion of subjects discontinuing treatment or study participation due to a safety concern. This rate will be defined as the number of subjects discontinuing from therapy or from the study over the total sample. Eligibility: Patients must have: Histologically/cytologically documented SCCHN, excluding nasopharyngeal carcinoma. Squamous cell carcinomas of unknown primary are allowed. Primary salivary gland tumors and tumors of the nasal cavity and paranasal sinuses are not included. Be ≥18 years of age. Evaluable or uni-dimensionally measurable local-regional and/or metastatic disease that is not amenable to primary surgical resection or radiotherapy (according to RECIST) Locally advanced or metastatic SCCHN. Patients Should have received no more than one trial of palliative chemotherapy after their curative therapy. Curative therapy could have included chemotherapy either in an induction chemotherapy form and/or chemoradiotherapy. Patients must have received a Platinum based regimen prior to enrolling on this protocol and could have received one Biliologocal A life expectancy of at least 3 months. An ECOG performance status of 0-2. Negative pregnancy test for women of childbearing potential Adequate bone marrow function (i.e., absolute granulocyte count ≥ 1500/mm³ and platelet count ≥ 100,000/mm³). Be available for follow-up. Patients must not have had: Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease ≥2 (see Appendix C) within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded. Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication. Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age. Presence of left bundle branch block (LBBB.) QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG. If a patient has QTc ≥480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the patient to be eligible for the study.) Any concomitant medication (within 14 days of starting treatment) that may cause QTc prolongation, induce Torsades de Pointes (see Appendix A) or induce CYP3A4 function. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg) Currently active diarrhea (CTCAE v3 > grade 2) that may affect the ability of the patient to absorb the ZACTIMA or tolerate diarrhea. Women who are currently pregnant or breast-feeding. Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in-situ and adequately treated basal cell or squamous cell carcinoma of the skin Receipt of any investigational agents within 30 days prior to commencing study treatment Last dose of prior chemotherapy discontinued less than 3 weeks before the start of study therapy Prior treatment with docetaxel Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy Previous enrollment or randomization of treatment in the present study Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy *If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.* 07-041 A Randomized, Open-Label, Controlled, Phase II Trial of Combination Chemotherapy with or without Panitumumab as First-line Treatment of Subjects with Metastatic or Recurrent Head and Neck Cancer, and Over-over Second-line Panitumumab Monotherapy of Subjects who Fail the Combination Chemotherapy Only Arm Objectives: The purpose of this study is to estimate the effect of panitumumab on progression free survival when added to combination chemotherapy in treatment of metastatic or recurrent squamous cell carcinoma of head and neck (SCCHN). The study will also examine response to treatment, and overall survival and safety of the treatment. Eligibility: Histologically or cytologically confirmed squamous cell carcinoma of the head and neck or its variants. Diagnosis of metastatic disease and/or recurrent disease. No prior systemic treatment for metastatic and/or recurrent SCCHN. No prior anti-EGFr therapy. No medical contraindication to therapy. If you have questions or would like further information about this trial, please contact Rafia Khan at (617) 582-8013. Chemoprevention 05-361 Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: a Randomized Phase IIb Trial Objective: The purpose of this study is to conduct a placebo-controlled, double-blind and randomized 6 month phase IIb cancer control chemoprevention trial of the Bowman-Birk Inhibitor Concentrate (BBIC) in patients with Oral Leukoplakia (OL). This study is being performed to determine whether a product made from soybeans named Bowman-Birk Inhibitor Concentrate (BBIC) affects oral precancerous lesions known as oral leukoplakia (white patch) or erythroplakia (red patch). These types of lesions sometimes, but not always, develop into oral cancer. One of the purposes of this research is to compare the effectiveness of BBIC to an inactive material (called a "placebo") to see if BBIC has any effect on these patches. Another purpose of the study is to see if there are any side effects when taking this medication. Eligibility: Patients must have clinically and histologically proven oral leukoplakia and/or erythroplakia and be ≥18 years of age. Women of childbearing potential must not be pregnant and must be willing to use adequate birth control methods. Patients will not be eligible if there has been the use of systemic steroids, or topical oral steroid preparations within three months of the study. *If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.* Trials for patients with recurrent disease 05-379 A Phase II, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Proxinum^® in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck Who Have Received At Least One Prior Anti-cancer Treatment Regimen for Recurrent Disease Primary objective: To determine the safety, tolerability, and recommended dose (RD) of intratumorally injected Proxinium^® in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) who have received at least one prior anti-cancer treatment regimen for recurrent disease. Secondary objectives: To evaluate principal target tumor and target tumor response rates following intratumoral injection of Proxinium^® To determine the time to progression of the principal target tumor following intratumoral injection of Proxinium^® To determine overall survival time associated with intratumorally injected Proxinium^® To determine progression-free survival as assessed by evaluation of the principal target tumor following intratumoral injection of Proxinium^® To confirm the pharmacokinetic (PK) profile of intratumorally injected Proxinium^® To assess immunogenicity of intratumorally injected Proxinium^® Eligibility: The patient must have histologically confirmed SCCHN. The patient must have immunohistochemically confirmed epithelial cell adhesion molecule (Ep-CAM)-positive SCCHN. The patient must have received therapy for their primary disease (ie, SCCHN) consisting of radiotherapy with or without surgery and with or without chemotherapy. Patients must have documented recurrent disease following therapy for their primary disease. Patients must have progressed on or after receiving at least 1 prior anti-cancer treatment regimen containing 1 or more anti-cancer agents (eg, chemotherapy, biologic therapy, or photodynamic therapy for their recurrent disease. *If you have questions or would like further information about this trial, please contact Sonia Kim at (617) 632-5587.* 04-358 A Phase II Study of Single-Agent Depsipeptide in Patients with Unresectable or Metastatic Squamous Cell Carcinoma of the Head and Neck Primary objective: The primary objective of this study is to evaluate the rate of disease control (i.e., achievement of complete response, partial response, or stable disease) of the single agent depsipeptide in patients with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck. Secondary objective: The secondary objective of this study is to evaluate the duration of response, time to progression, and overall survival for patients with incurable head and neck cancer treated with depsipeptide. Eligibility: To be eligible for the study, patients must fulfill all of the following criteria: Histologically or cytologically confirmed squamous cell cancer of the head and neck that must be incurable with surgery or radiation therapy. No nasopharyngeal primaries The tumor should preferably be present at the primary site, and it must be accessible for biopsy Patients may have received up to one prior systemic chemotherapy regimen for unresectable, recurrent or metastatic disease. Chemotherapy must have been completed at least 4 weeks prior to entry into the study. Patients treated previously with mitomycin C and nitrosoureas should have a therapy-free interval of at least 6 weeks duration prior to study entry. If patients have received doxorubicin in the past, their cumulative dose of doxorubicin should not be more than 450 mg/m². Palliative radiation therapy is allowed but must have been completed at least 4 weeks prior to study entry. However, any primary, curative intent radiotherapy with or without chemotherapy must have been administered at least 6 months prior to study entry; in this case, patients may not have any prior chemotherapy for their recurrent disease. If the only site of measurable disease is a previously irradiated area, the patient must have documented progressive disease or biopsy-proven residual carcinoma. Persistent disease after radiotherapy must be biopsy-proven at least 8 weeks after the completion of radiotherapy. No prior biologic therapy No prior therapy with depsipeptide or other investigational agents/ drugs known to have histone deacetylase inhibitor activity such as sodium valproate. ≥18 years of age. Life expectancy of greater than 3 months. No significant cardiac disease including congestive heart failure or history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias, history of cardiac hypertrophy or poorly controlled angina. No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix. Patients with prior malignancies who have been disease-free for more than 2 years are eligible. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. A negative serum pregnancy test is required less than 2 weeks of randomization for women who are still menstruating. Patients may not be co-medicated with an agent that causes QTc prolongation or hydrochlorothiazide (HCTZ) No other serious uncontrolled illnesses or medical conditions No patients with immune deficiency that are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with depsipeptide. *If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.* 06-111 Randomized Phase II Study of Bevacizumab/Tarceva^® and Tarceva^®/Sulindac in Squamous Cell Carcinoma of the Head and Neck Primary Objective: The primary objective of this randomized Phase II study is to evaluate the efficacy of erlotinib (also called Tarceva^®) plus bevacizumab (also called Avastin^®) (Arm A) or erlotinib (Tarceva^®) plus sulindac (Arm B) in subjects with incurable recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN), as measured by progression-free survival (PFS). Secondary Objective: Secondary objectives include: evaluation of the overall response rate (ORR) of erlotinib (Tarceva^®) plus bevacizumab (Avastin^®) or sulindac in subjects with incurable SCCHN; evaluation of the duration of overall survival and objective response with erlotinib (Tarceva^®) plus bevacizumab (Avastin^®) or sulindac in this patient population (rates of PFS at 4 months and 1 year will also be determined); evaluation of the safety and side effects of erlotinib (Tarceva^®) plus bevacizumab (Avastin^®) or sulindac in subjects with incurable SCCHN; and to bank pre- and post-treatment tissue specimens in a subset of subjects for exploration molecular markers associated with response. Eligibility: Subjects must be 18 years of age or older with histologically/ cytologically documented squamous cell carcinoma of the head and neck. Subjects must have evaluable locoregional and/or metastatic disease that is not appropriate for treatment by primary surgical resection or radiotherapy. Subjects must have failed to respond to or relapsed from at least once prior chemotherapy or chemoradiotherapy. Subjects will be excluded from this study if they have had: more than one prior systemic therapy for recurrent and/or metastatic disease, any other malignancy within 5 years (except non-melanomatous skin cancer, or carcinoma in situ of the cervix, bladder or head and neck), concurrent anticancer therapy (other than that of this study), treatment with any anticancer drug within 28 days of beginning this study, radiotherapy within 28 days of beginning this study, any prior therapy which targets the ErbB and/or VEGF pathways (including oral kinase inhibitors and antibody therapy), concurrent therapy with any NSAID (except aspirin at a dose of no more than 81 mg per day), known hypersensitivity characterized by acute bronchospasm, urticaria and/or rhinitis to NSAIDs (including aspirin). Subjects will also be excluded form this study if they have other serious illnesses or medical conditions, a tumor that encases the carotid artery (or other major vessel that in the opinion of investigators is at risk for tumor-related hemorrhage), or have the presence of central nervous system or brain metastases. *If you have questions or would like further information about this trial, please contact Rafia Khan at (617)582-8013.* 06-179 A Pilot Feasibility Study of Epstein-Barr Virus-Specific Immunotherapy for Nasopharyngeal Carcinoma Objectives: The primary objective for this Pilot study is to determine the feasibility and safety of generating and administering at least 2 infusions of Epstein-Barr Virus (EBV)-specific adoptive T cells in subjects with incurable locoregional relapsed and/or distant metastatic EBV-associated nasopharyngeal carcinoma (NPC). The data collected from this Pilot study will provide the basis for a Phase II study to establish the clinical efficacy of EBV-specific adoptive immunotherapy for the treatment of NPC. Basic science studies aimed at understanding the mechanisms underlying effective EBV-specific immunotherapy will also be initiated in this Pilot study and should allow more advanced studies of specific EBV-associated immune factors in a future Phase II clinical trial. Eligibility: Histologically or cytologically proven NPC of any WHO grade associated with EBV as documented by the presence of EBER by immunohistochemistry in the tumor. Incurable NPC as defined by relapsed or progressive disease at the primary site and/or regional lymph nodes after initial treatment with no potential curative option OR NPC with distant metastasis. Age > 18 years and ECOG Performance Status ≤ 1. No prior radiotherapy for primary NPC within 8 weeks of enrollment or chemotherapy for NPC within 2 weeks of enrollment. No other cancer within 5 years, with the exception of carcinoma in situ of the cervix or bladder, or non-melanoma skin cancer. No uncontrolled central nervous system metastases. Certain significant medical conditions may be exclusionary. *If you have questions or would like further information about this trial, please contact Jayme Flynn at (617) 632-5260.* Thyroid Cancer 06-188 A Phase II, Open-Label Study to Assess the Efficacy and Tolerability of ZD6474 (ZACTIMA) 100 mg Monotherapy In Subjects with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer. Objective: The primary objective of this study is to determine the objective response rate in subjects treated with ZD6474 monotherapy. Secondary objectives are to determine the safety and tolerability of ZD6474 treatment in this patient population, to determine the progression free survival of hereditary MTC in subjects following ZD6474 100 mg therapy, as well as the disease control rate, duration of objective response, and duration of disease control with ZD6474. Secondary objectives also include assessment of performance status as well as bowel frequency changes during therapy, in addition to an assessment of the effect of ZD6474 on calcitonin and CEA levels, and to characterize the population pharmacokinetic of ZD6474 in subjects with hereditary MTC. Eligibility: Potiential subjects must be over 18 years of age, WHO Performance status of 0-2, at least one measureable lesion greater than 1 cm on spiral CT, and women of childbearing potential must have a negative pregnancy test. Only subjects with the hereditary form of medullary thyroid cancer will be eligible for entry into this trial. Subjects must not have brain metastases or spinal cord compression, unless irradiated at least four weeks before the first dose and stable without steroid treatment for greater than one week. Subjects must have had their last surgical procedure, dose of chemotherapy or radiation, at least four weeks before starting study. Subjects must not have significant cardiac issues that put them at risk of ventricular arrhythmia, or asymptomatic sustained ventricular tachycradia, or congenital long QT syndrome, or first degree relative with unexplained death under 40 years of age. Subjects cannot have a left bundle branch block, uncontrolled hypertension, previous malignancies at other sites within five years of study start, with the exception of in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin. Compensation: There may be funds available to aid any patient who wishes to participate, but will require a large travel expenditure. Details regarding travel reimbursement may be discussed further with the study staff. *If you have questions or would like further information about this trial, please contact Jeff Miller at (617) 632-2503.* 06-252 A Phase II, Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study to Assess the Efficacy of ZD6474 (ZACTIMA) versus Placebo in Subjects with Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer Objective: This will be a Phase II, randomized study to establish the effect of once-daily oral doses of ZD6474 300mg vs placebo in subjects with locally advanced or metastatic hereditary or sporadic medullary thyroid cancer in whom no standard therapeutic option is available. It will be conducted in a minimum of 232 subjects in approximately 58 countries. The subjects may continue with ZD6474 as long as they are receiving clinical benefit or until they are given another anti-cancer therapy. Eligibility: To participate in study you must: Be 18 years or older ; Have confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic MTC ; Have a measurable tumor; Be able to swallow medication You are not able to participate if you have: Had major surgery within 4 weeks before randomization; Received the last dose of prior chemotherapy less than 4 weeks prior to randomization; Had radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy); Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days; Significant cardiac events; Had previous ZD6474 treatment *If you have questions or would like further information about this trial, please contact Jeff Miller at (617) 632-2503.* 06-321 A Pivotal Phase 2 Study of the Anti-Angiogenesis Agent AG-013736 in Patients with ¹³¹I-refractory metastatic or Unresectable locally-advanced papillary, follicular, or Hurthle-cell thyroid cancer who are also refractory to, or intolerant of, or have clinical contraindication to, doxorubicin treatment Primary Objective: The primary objective of this study is to determine the objective response rate (ORR) of patients with ¹³¹I-refractory metastatic or unresectable locally-advanced papillary, follicular, or Hurthle-cell thyroid cancer who are also refractory to, or intolerant of, or have clinical contraindication to, doxorubicin treatment. Inclusion Criteria: Histologically documented, ¹³¹I-refractory metastatic or unresectable locally-advanced thyroid cancer of papillary, follicular or Hurthle cell histology. Failure of doxorubicin (either as a single agent or in combination with other agents) to control the disease, documented with radiographic evidence of disease progression as defined by RECIST criteria and documented with 2 sets of CT/MRI scans or 2 sets of chest x-rays during doxorubicin therapy or within 6 months after the last dose of doxorubicin (scans or chest x-rays must be received and verified by imaging core laboratory before patient can receive treatment); Intolerance of doxorubicin therapy, defined as occurrence of life-threatening or grade 4 toxicity attributable to previous therapy with doxorubicin (a maximum of 10 patients will be eligible under this criteria); Doxorubicin therapy is clinically contraindicated, defined as patients who have received a cumulative doxorubicin dose of >450 mg/m² during previous therapy. If a patient has only locally-advanced cancer without distant metastasis, in addition to satisfying the above inclusion criteria, the disease must also be unresectable (eg, tumor involving vital structure, history of previous surgery in the same area, or concurrent severe medical condition that prevents surgery) AND must be refractory to external beam radiotherapy. At least 1 measurable target lesion, as defined by RECIST. If the only measurable target lesion is located in an externally irradiated field, this lesion may be used as measurable disease only if the lesion diameter has grown by≥20 % since completion of the prior external irradiation or if the lesion is a new lesion, assuming all other criteria are met (CT/MRI scans must be received and verified by imaging core laboratory before patient can receive treatment). Baseline scans must be received by the imaging core laboratory before the patient can receive treatment with AG-013736. Adequate hepatic, and renal function documented within 14 days prior to treatment as documented by: AST and ALT ≤2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT ≤5.0 x ULN total bilirubin ≤1.5 x ULN serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min urinary protein <2+ by urine dipstick. If dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours Age ≥18 years. ECOG performance status of 0 or 1 (see Appendix D) No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140, and the baseline diastolic blood pressure readings must be ≤90. Patients whose hypertension is controlled by antihypertensive therapies are eligible. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to treatment. Exclusion Criteria: Central lung lesions involving major blood vessels (arteries or veins). (Central lesions that maintain the structural integrity of vessels have the potential to bleed if the tumor lesion undergoes necrosis. MRI or CT angiography should be used in any case where there is any question as to whether blood vessels are involved.) Thyroid lymphoma or anaplastic or medullary histology Bleeding from lung (as evidenced by hemoptysis) > 1/2 tsp of bright red blood per day within past 1 week Gastrointestinal abnormalities including: inability to take oral medication requirement for intravenous alimentation prior surgical procedures affecting absorption including gastric resection treatment for active peptic ulcer disease in the past 6 months active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy. malabsorption syndromes. Previous treatment with anti-angiogenesis agents including thalidomide, Sutent (SU-011248), AMG 706, sorafenib, and bevacizumab. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine). Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John's wort). Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism. History of a malignancy (other than thyroid cancer) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years Major surgical procedure within 4 weeks of treatment. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Patients (male and female) having procreative potential who are not using adequate contraception or practicing abstinence. Women who are pregnant or breast-feeding. *If you have questions or would like further information about this trial, please contact Rafia Khan at (617) 582-8013.* Phaseone Phase I Trials 06-416 An Open-Label, Randomized, Phase 1b Study Evaluating the Effect of Different Doses of AMG 706 on the Gallbladder in Subjects with Advanced Solid Tumors Primary Objective: The primary objective of this study is to evaluate the effect of AMG 706 monotherapy administered according to three different dosing schemes on the change in size (volume) and function (eject fraction) of the gallbladder. Secondary Objective(s): To evaluate overall changes in selected other gallbladder characteristics (e.g. length, width, height, area, wall thickness, and ductal dilation/size, To evaluate reversibility of the size (volume) and function (eject fraction) of the gallbladder following withdrawl of AMG 706, To evaluate the pharmacokinetics of AMG 706 at various dosing schemes in all three treatment arms, To evaluate the safety and tolerability of AMG 706 in all three treatment arms, and To evaluate objective response rates in subjects with advanced solid tumors receiving AMG 706 monotherapy. Eligibility: Key Inclusion Criteria: Histology confirmed advanced metastatic solid tumor Ineligible to receive or progressed on standard of care therapies Measurable or non-measurable disease per modified RECIST (Response Evaluation Criteria in Solid Tumor) Gallbladder must be in situ on screening ultrasound ECOG Performance Status of 0 to 2 Life expectancy of > 6 months as determined by the investigator Adequate organ and hematological function as evidenced by laboratory studies prior to randomization Men and women > 18 years old Key Exclusion Criteria: Uncontrolled central nervous system metastases Known history of prior episodes of cholecystitis, prior biliary procedure (ie, ERCP, biliary stent), or prior or on-going biliary disease Radiation therapy within 14 days prior to randomization Peripheral neuropathy > grade 1 per Common Terminology Criteria for Adverse Events (CTCAE version 3.0) Currently or previous treated with AMG 706, or other small molecule inhibitors of VEGF including, but not limited to, SU11248 (sunitinib), PTK787 (vatalanib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib), ZD6474 (vandetanib) Subjects who have been previously treated with bevacizumab will be permitted if at least 6 weeks (42 days) have elapsed from the last dose of bevacizumab to the date of randomization Any anticoagulation therapy within 7 days prior to randomization. The use of low-dose warfarin [<2 mg daily] or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis is allowed Less than 30 days since ending an investigational device or drug trial from randomization, or currently receiving other investigational treatments History of arterial or venous thrombosis within 1 year prior to randomization History of bleeding diathesis or bleeding within 14 days of randomization Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, grade 2 or greater peripheral vascular disease, arrythmias not controlled by outpatient medication, or unstable angina within 1 year prior to randomization Uncontrolled hypertension as defined by resting blood pressure > 150/90 mm Hg. Anti-hypertensive medications are allowed if the medications are allowed if the subject is stable at the time of randomization Surgery: Major surgical procedure within 4 weeks (28 days) prior to randomization Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of randomization Planned elective surgery while on study Non-healing or open wound, ulcer, or fracture Known ongoing or active infection Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen Known chronic hepatitis Known history of allergic reaction or hypersensitivity to AMG 706 or any of its components Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding For further information on this study, please contact the research coordinator for this trial, Jayme Flynn at (617) 632-5260. Phase I/II Trial of Abraxane in Combination with Carboplatin, Erbitux and Intensity Modulated Radiation Therapy (IMRT) for Treatment of Locally Advanced Squamous Cancer of the Head and Neck Objectives: The primary objective for the phase I portion of this clinical trial is to identify the maximally tolerated dose of Abraxane given with carboplatin and Erbitux plus concurrent IMRT (ACE-RT) for locally advanced SCCHN. I In the phase II portion of the study, the objective is evaluate the efficacy of this regimen by evaluating 2-year disease-free survival. The secondary objectives are to evaluate the safety and tolerability of the combination of Abraxane, carboplatin and Erbitux, to estimate the overall response rate to ACE-RT, to estimate 2-year overall survival, and to evaluate functional outcome at 2 years with respect to speech, swallowing and overall quality of life . Eligibility: Histologically or cytologically proven squamous cell carcinoma of the head and neck. Eligible sites: oral cavity, oropharynx, nasopharynx, hypopharynx, larynx or unknown primary site. Stage III or IV disease without evidence of distant metastases. At least one uni- or bi-dimensionally measurable lesion. Age > 18 years. No previous surgery, radiation therapy or chemotherapy for SCCHN (except biopsy or tonsillectomy). No previous or current malignancies at other sites, with the exception of non-melanoma skin cancer, carcinoma in situ of the cervix, bladder or head and neck. No prior therapeutic radiation to the head and neck. No prior therapy which targets the EGFR pathway. *If you have questions or would like further information about this trial, please contact Jeff Miller at (617) 632-2503* Non-protocol Non-protocol treatments Salivary gland cancer/adenoid cystic carcinoma: Second line chemotherapy with Cytoxan, Adriamycin and Oxaliplatin for patients who have not had prior exposure to these three drugs and who have progressed on other chemotherapy for metastatic or recurrent disease. Cycles are every 3-4 weeks. Recurrent or metastatic nasopharynx cancer: First line salvage for possible cure. ABIM (Adriamycin, Bleomycin, Ifosfamide and Mesna). Patients with metastatic disease, or locally recurrent disease for which further radiation is not recommended, no prior systemic chemotherapy for recurrence, no radiation to sites outside the head and neck. This therapy requires hospitalization for 4 days, a venous access device and careful monitoring. Cycles are every three to four weeks. Radiotherapy is planned for limited stage recurrences.	Disease-based Programs Breast Cancer Cutaneous Oncology and Melanoma Gastrointestinal Malignancies Gynecologic Cancer Head and Neck Cancer - Members - About Our Program + Clinical Trials - Becoming a Patient - Links for Patients - Scientific Publications - Contact Kidney Cancer Leukemia Lung Cancer Lymphoma and Myeloma Neuro-Oncology Prostate Cancer Sarcoma Discipline-based Programs Joining a Program
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Investigational Curative Therapy

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Chemoprevention

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Trials for patients with recurrent disease

05-379 A Phase II, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Proxinum® in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck Who Have Received At Least One Prior Anti-cancer Treatment Regimen for Recurrent Disease

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06-111 Randomized Phase II Study of Bevacizumab/Tarceva® and Tarceva®/Sulindac in Squamous Cell Carcinoma of the Head and Neck

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Thyroid Cancer

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Phaseone

Phase I Trials

06-416 An Open-Label, Randomized, Phase 1b Study Evaluating the Effect of Different Doses of AMG 706 on the Gallbladder in Subjects with Advanced Solid Tumors

Primary Objective:

Secondary Objective(s):

Eligibility:

Key Inclusion Criteria:

Key Exclusion Criteria:

Non-protocol

Non-protocol treatments

Salivary gland cancer/adenoid cystic carcinoma:

Recurrent or metastatic nasopharynx cancer:

05-379 A Phase II, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Proxinum^® in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck Who Have Received At Least One Prior Anti-cancer Treatment Regimen for Recurrent Disease

06-111 Randomized Phase II Study of Bevacizumab/Tarceva^® and Tarceva^®/Sulindac in Squamous Cell Carcinoma of the Head and Neck