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Trials for patients with 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

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.

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08-146

ImClone : A Randomized Phase 2 Open-Label Study of IMC-A12, as a SingleAgent  or in Combination With Cetuximab, in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head  and Neck and Disease Progression on Prior Platinum-Based Chemotherapy

Primary Objectives:

To assess median progression-free survival (PFS) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have experienced disease progression on at least one prior platinum-containing chemotherapeutic regimen, when treated with IMC-A12 monotherapy or

IMC-A12 and cetuximab combination therapy.

Secondary Objectives:

• To determine the objective response rates (ORR)

• To determine the 6-month PFS rates

• To determine the overall survival rates

• To determine the duration of response

• To evaluate the safety, tolerability, and adverse event profiles of these therapeutic regimens in the treatment of recurrent or metastatic SCCHN

• To assess blood and tissue biomarkers and the development of serum antibodies against IMC-A12 and cetuximab

Eligibility:

Each patient must meet the following criteria to be enrolled in this study:

• The patient has histologically or cytologically-confirmed squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity, metastasis or recurrence documented by clinical imaging studies.

• The patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), with minimum lesion size ≥ 2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan.

• The patient has clinical documentation of disease progression during treatment with or within90 days after receiving the last cycle of platinum-based chemotherapy (with or without radiation therapy).

•  If the patient has received prior treatment with anti-EGFR therapy, the time to recurrence from last anti-EGFR therapy is > 90 days

• The patient is age ≥ 18 years.

• The patient has a life expectancy of > 3 months.

• The patient has an Eastern Cooperative Oncology Group performance status of 0-2.

• The patient has adequate hematologic function as defined by absolute neutrophil count ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and platelet count ≥ 100,000/μL.

• The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases).

•  The patient has either adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) no more than 5seconds above the ULN or is on a stable dose of an anticoagulant.

• The patient has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 mL/min for patients with creatinine levels above the ULN.

• The patient has fasting serum glucose <120 mg/dL or below the ULN.

• Because the teratogenicity of IMC-A12 is unknown, 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.

• The patient has the ability to understand and the willingness to sign a written informed consent document.

For Further Information Regarding this study please contact Britta Andreozzi at:  (617) 582-8039.

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08-292

NPC :   Epstein-Barr Virus-Specific Adoptive Immunotherapy for Nasopharyngeal Carcinoma: A Phase II Trial

Primary Objectives:

The primary clinical objective of this study will be to determine the overall response rate of EBV-specific immunotherapy in patients with recurrent and/or metastatic EBV-associated NPC.

Secondary Objectives:

• To estimate the one year PFS, time to progression, median duration of response and overall survival with EBV-specific immunotherapy

• To evaluate the safety of EBV-specific immunotherapy

• To explore the potential benefits of immunomodulatory manipulation during the T cell manufacturing process

• To evaluate the biologic correlates of response to therapy.

Eligibility:

Each patient must meet the following criteria to be enrolled in this study:

• Histologically or cytologically proven NPC of any WHO grade, associated with EBV infection documented by the presence of EBER expression by in situ hybridization in the tumor. Other confirmation of EBV-associated disease is acceptable, such as EBV DNA in situ hybridization, if EBER analysis is not adequate.

• Incurable NPC, as defined by:

Relapsed or progressive disease at the primary site and/or regional lymph nodes after initial treatment (e.g. radiotherapy or chemoradiotherapy) with no potentially curative option (i.e. surgery or radiation); OR

NPC with distant metastasis;

• Performance Status 0 

• Recovery from toxicity from any prior NPC therapy to National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0) to grade 1 or better (except for alopecia, xerostomia, dysphagia, or mucositis);

• Age ³ 18 years;

• Evaluable or Measurable disease, according to modified RECIST

• Eastern Cooperative Oncology Group performance status (ECOG PS) £ 1. Special attention must be made to assure the patient has an accurate performance status.

• Adequate bone marrow, liver and renal function, defined by:

Hemoglobin ³ 8 g/dL;

Absolute neutrophil count (ANC) ³ 1500/mL;

Absolute lymphocyte count ³ 400/mL;

Platelet count ³ 100,000/mL;

ALT and AST £ 3 X upper limit of normal (ULN);

Total bilirubin £ 2 X ULN; and

Serum creatinine £ 2.0 X ULN;

• Women of child-bearing potential (WOCBP) must be willing to use acceptable means of birth control;

• No autoimmune disorders, immunosuppressive medications,, significant co-morbidities

• Signed informed consent.

For Further Information Regarding this study please contact Britta Andreozzi at    1-617-582-8039

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Phase I Trials

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07-069

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 John Fasciano at (617) 632-7323.

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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:

1.      To evaluate the safety and tolerability of the combination of Pan-CRT

2.      To evaluate the safety and tolerability of Pan-TPF

3.      To estimate the overall response rate (ORR) to Pan-TPF

4.      To estimate the ORR of sequential therapy

5.      To estimate the rate of pathologic complete response (pCR) of primary tumor biopsy after Pan-TPF

6.      To estimate 2-year disease free survival (DFS)

7.      To estimate 2-year overall survival (OS)

8.      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.

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08-169    Acupuncture for Dysphagia after Chemoradiation Therapy in Head and Neck Cancer Patients: A Pilot Randomized Controlled Trial Protocol.

Objectives:

This study is a pilot randomized, controlled trial of acupuncture for Head and Neck Cancer patients with dysphagia after chemoradiation therapy. The study will assess the feasibility of recruiting and retaining head and neck cancer patients, will assess the feasibility of administering the acupuncture protocol as well as a series of outcome instruments and protocols, and will collect preliminary data on the efficacy and safety of acupuncture on dysphagia related symptoms and health related quality of life. Following successful completion of eligibility requirements participants will be randomized to either active acupuncture or inactive acupuncture. The study will require weekly acupuncture for 12 weeks and a 6 month follow up visit during which study patients will be asked to fill out several questionnaires.

Eligibility:

Inclusion Criteria:

• Histologically or cytologically proven squamous cell carcinoma of the head and neck (SCCHN) at stage II, III, and IV, without evidence of distant metastasis
• Primary tumor sites eligible: nasopharyngeal, oropharynx, hypopharynx or larynx. Tumors of the nasal and paranasal cavities will also be included. Unknkown primary squamous cell carcinoma in the neck will also be eligible;
• Completed radiation therapy, beginning 8-12 weeks, up to 20 weeks;
• No measurable, persistent, or recurrent tumor that is ascertained by a formal restaging process by the study team
• Currently or recently undergoing swallowing therapy program with or without feeding tube use, with or without neck dissection;
• Age >= 18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Adequate hematological function: neutrophil count > 1.0x10^9/L, platelet count > 50x10^9/L;
• Signed informed consent.

Exclusion Criteria:

Patients with the following criteria will NOT be eligible for the study:

• SCCHN patients with tumor site at oral cavity
• SCCHN patients enrolled in other investigational trials
• Unstable cardiac disease or myocardial infarction within 6 months prior to study entry;
• Wearing a pacemaker or implantable cardioverter-defibrillator;
• History of significant neurologic disorder that affects swallowing, including stroke, neurodegenerative disease, advanced dementia, or uncontrolled seizure disorder;
• Active clinically significant uncontrolled infection;
• Prior use of acupuncture for dysphagia

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

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Non-protocol treatments

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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.