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Research Programs

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Translational Pharmacology and Early Therapeutic Trials

Clinical Trials

Clinical Trials

Statement of Priorities

 

The principal priority of the DF/HCC Translational Pharmacology is to develop new and effective treatments for cancer. The Programs priorities for bringing an agent into trials at the DF/HCC are: the strength of the experimental and pre-clinical data supporting potential efficacy; agents with high-value novel targets that could be expected to have a significant impact on the future of cancer therapeutics; agents that have a translational and pharmacokinetic component that can be performed at the DF/HCC; first in human trials; agents that DF/HCC Disease Programs would value for phase II trials; agents that have been developed with significant intellectual contribution from the DF/HCC investigators or in which basic investigators have a special interest; and studies that can be performed exclusively at the DF/HCC.

Active Studies

As of April 16, 2009

SIGNAL TRANSDUCTION

C-met Inhibitors:

  1. 06-074 (Exelixis) - XL880 -c-met/KDR/PDGFR/Tie-2/flt-3 inhibitor / continuous dosing schedule
  2. 08-007 (MethlyGene) - MGCD265 - Combined c-met and VEGFR2 inhibitor
  3. 08-093 (Exelixis) - XL184 + Tarceva
  4. 08-157 (Pfizer) - C-met inhibitor (no Alk inhibition)

C-met/Alk Inhibitors:

  1. 06-068 (Pfizer) - PF-02341066 c-met/HGFR aminopyridine tyrosine kinase inhibitor and potent ATP-competitive inhibitor of recombinant, human c-met/HGFR kinase/ activity against Alk-1

EGFR/ErbB Family Inhibitors:

  1. 07-189 (Aveo) AV-142 - Oral irreversible pan-erbB inhibitor with activity against HSp 90
  2. 08-171 (Boehringer Ingelheim) - BIBW2992 in genetically screened tumors.
  3. 08-175 (Merrimack) - MM121 - ERBB3 Antibody

PI3K Inhibitors:

  1. 07-112 (Exilixis) XL147 -  Oral PI3 kinase inhibitor
  2. 07-239 (Novartis) BEZ235  - Oral PI3 kinase inhibitor
  3. 07-263 (Genentech) GDC-0941 - Oral PI3 kinase inhibitor
  4. 08-041 (Novartis) BGT226 - Oral PI3 kinase/mTOR inhibitor
  5. 08-327 (Exelixis) XL765 + Tarceva

Mek Inhibitor:

  1. 09-005 (AstraZeneca) AZD6244 in non-melanoma B-Raf mutant tumors

 TGF-beta Inhibitors:

  1. 06-151 (Genzyme) - GC1008 - human anti-TGF-beta 1,2,3 monoclonal antibody/ IgG4

Notch Inhibitors:

  1.  07-311 (Roche) RO4929097 - Notch Inhibitor/ Gamma Secretase Inhibitor

Hsp90 Inhibitors:

  1. 07-151 (Synta) - STA-9090 - Hsp90 inhibitor
  2. 07-174 (Novartis) - AUY922 - Hsp90 inhibitor, pyrazole class
  3. 08-006 (Astex) - AT13387 - Hsp90 inhibitor

Fak Inhibitors:

  1. 08-383 (Pfizer) - Focal Adhesion Kinase Inhibitor, oral

ANGIOGENESIS

  1. 04-385 (Pfizer/Lilly) - Sunitinib/Gemcitabine

CELL CYCLE

Cyclin-Dependent Kinases:

  1. 02-243 (Esai) E7070 and irinotecan - CDK inhibitor with indirect effects on CDKs (mainly CDK9) and Rb phosphorylation
  2. 03-082 (NCI/CTEP) - Flavopiridol - CDK inhibitor -short infusion schedule in Cyclin D1 expressing tumors
  3. 03-110 (NCI/CTEP) - Flavopiridol/ Gemcitabine - short infusion schedule
  4. 06-301 (Schering) - SCH727965 - CDK 1,2 and 9 inhibitor
  5. 06-380 (Pifzer) - PD0332991 - Cdk4 inhibitor in Mantle Cell Lymphoma (PK Study)

Aurora Kinases:

  1. 06-047 (AstraZeneca) - AZD-1152 - Selective Aurora Kinase B Inhibitor
  2. 07-399 (EntreMed) - EMND-2076 - Aurora A and VEGFR inhibitor

DNA DAMAGE MODULATION

Checkpoint Kinase Inhibition

  1. 06-414 (Takeda/ BMS) - CBP-501 with CDDP - chk1/ck2 inhibitor with DNA damaging agent
  2. 07-040 (AstraZeneca) - AZD7762, a small molecule chck1 inhibitor with CPT11
  3. 08-121 (Abbott, NCI- CTEP) - ABT888 + CPT11 - PARP inhibitor plus chemotherapy
  4. 08-030 (Merck) - Wee1 Inhibitor + chemotherapy
  5. 08-239 (AstraZeneca) - AZD2281 plus Kudos PARP inhibitor + chemotherapy

PROTEIN STABILITY

  1. 08-161 (Millennium/Takeda) - MLN4824 - Inhibitor of NEDD8 activating enzyme

BCL-2/BCL-xL INHIBITION

  1. 06-369 (Abbott) - ABT263 - in small cell lung cancer and other solid tumors

MISCELLANEOUS/ CYTOTOXICS

  1. 08-033 (AMRI) - ALB109564 - Novel Vinca Alkaloid
  2. 08-197 (Taiwan Liposome Co) - Novel Topoisomerase 1 Inhibitor

DF/HCC Agenda

The Translational Pharmacology Program will continue to seek new agents that are in keeping with our priorities. It is a major interest of our academic research mission to emphasize translational studies that utilize the resources available at the Df/HCC. The Molecular and Cancer Imaging groups, the Pharmacology Core Laboratory, and independent basic science investigators with a special interest that can be converted into a translational study with actual patient tissue are the areas of particular emphasis.

Mechanics of How We do Trials

  • Open at all DF/HCC sites (hospitals).
  • Capable of collecting & distributing samples.
  • Work closely with the Cancer Pharmacology Core which has the capability of doing sophisticated pharmacokinetics.
  • We have a very active ongoing effort with respect to anti-angiogenic compounds, signal transduction inhibitors and immmuno-therapies (vaccines).

Clinical Trials Accrual

The majority of trials are actively accruing patients at all DF/HCC institutions.

  • Currently we have 37 trials open.
  • In 2005 we accrued 151 patients in therapeutic studies.
  • In 2006 we accrued 124 patients in therapeutic studies
  • In 2007 we accrued 184 patients in therapeutic studies.

We are interested in opening all trials at all sites.

An analysis of accrual patterns by Cancer Center site was performed. Of the Phase I and II studies that accrued 10 or more subjects (excluding Pediatric, Proton Beam, and Cooperative Group Studies), 82% of eligible protocols in this disease program were multi-institutional in accrual by these criteria. 91% of the studies conducted by this program are Phase I studies.