Clinical Trials

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 June 16, 2011

SIGNAL TRANSDUCTION

c-Met Inhibitors:

1. 08-007 (MethlyGene) - MGCD265 - Combined c-met and VEGFR2 inhibitor
2. 09-432 (Exilixis) - XL184 - c-met, VEGFr, c-Ret Inhibitor)

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. 08-171 (Boehringer Ingelheim) - BIBW2992 in genetically screened tumors.
2. 08-175 (Merrimack) - MM121 - ERBB3 Antibody
3. 09-036 (Wyeth/ Pfizer) - HKI-272 +CCI779 - EGFR, Her2 inhibitor combined with mTOR inhibitor
4. 10-257 (Genentech) - MEHD7945A - Monoclonal antibody targets both EGFR and ERBB3.
5. 10-275 (Abbott) - ABT806 - Antibody agains EGFRvIII

FGFR Inhibitors:

1. 10-446 (Novartis) - BGJ398 -  FGFR inhibitor

PI3K Inhibitors:

1. 07-112 (Exilixis) - XL147 -  Oral PI3 kinase inhibitor
2. 07-239 (Novartis) - Patients with PIK3CA mutation
3. 09-215 (Pfizer) - PKI-587 (PF-05212384) - Dual PI3K/mTOR inhibitor - intravenous
4. 09-309 (Genentech) - GDC-0941 + GDC-0973 - Oral PI3 K inhibitor + oral MEK inhibitor
5. 10-110 (Zenyaku) - ZSTK474
6. 10-262 (Novartis) - BYL719 - PI3K inhibitor - alpha isoform specific
7. 11-010 (Genentech) - GDC-0032

RAF-MEK-ERK Inhibitors:

1. 09-005 (AstraZeneca) - AZD6244 in non-melanoma B-Raf mutant tumors
2. 10-056 (GSK) - BRAF inhibitor GSK2118436 in combination with MEK inhibitor GSK1120212 in B-raf mutant melanoma (and other cancers)

Stem Cell Pathways:

1. 09-038 (Pfizer) - PF-03084014 - Notch Inhibitor
2. 10-261 (Takeda/Millennium) - Hedgehog Inhibitor

Hsp90 Inhibitors:

1. 07-151 (Synta) - STA-9090 - Hsp90 inhibitor
2. 08-006 (Astex) - AT13387 - Hsp90 inhibitor

Fak Inhibitors:

1. 08-383 (Pfizer) - PF04554878 Focal Adhesion Kinase Inhibitor, oral

ANGIOGENESIS

1. 09-057 (BMS) - Brivanib and chemotherapy (Xeloda, Doxorubicin, Ixabepillone, Taxotere, Taxol) 
2. 09-207 (GSK) - Pazopanib in organ dysfunction
3. 10-021 (Mersana) - XMT-1107 - Fumagillin conjugate linked to a polymer
4. 10-166 (GSK/Novartis) - Pazopanib + RAD001 in GU malignancies and other solid tumors

CELL CYCLE

Cyclin-Dependent Kinases:

1. 03-082 (Sanofi) - Flavopiridol - CDK 1,2,4,6,7, 9 inhibitor - bolus followed by short infusion schedule in Cyclin D1 expressing tumors.
2. 08-271 (Cyclacel) - Sapacitabine (nucleoside analog) and Seliciclib (cdk inhibitor)
3. 10-017 (Lilly) - LY2835219 - CDK4,6 inhibitor
4. 10-383 (Novartis) - LEE011 - cdk 4/6 inhibitor, Rb-positivity required

Aurora Kinases:

1. 09-243 (Millennium/ The Takeda Company) - TAK901 - pan inhibitor of Aurora Kinases

DNA DAMAGE MODULATION

Checkpoint Kinase Inhibition

1. 07-040 (AstraZeneca) - AZD7762, a small molecule chck1 inhibitor with CPT11
2. 08-121 (Abbott, NCI- CTEP) - ABT888 + CPT11 - PARP inhibitor plus chemotherapy
3. 08-030 (Merck) - Wee1 Inhibitor + chemotherapy

OTHER ORGAN DYSFUNCTION STUDIES

1. 10-162 (Sanofi-Aventis) - Cabacitaxel in liver dysfunction 

PROTEIN STABILITY

1. 08-161 (Millennium) - MLN4824 - NEDD8 Inhibitor

BCL-2/ BCL-xL Inhibitor

1. 09-253 (Abbott) - ABT263 in combination with Gemcitabine
2. 07-348 (Lilly) - Pemetrexed + LY573636 - inhibits mitochondrial ATP generation

FMS  Inhibitor

1. 09-307 (Plexxikon) - PLX3392 - Inhibitor of Fms, c-kit and Flt3

STAT3  Inhibitor

1. 10-096 (Otsuka) - OPB-51602 - STAT3 Inhibitor

RNAI THERAPEUTICS

1. (Alnylam) - ALN-VSP-02 - SNALP (Stable Nucleic Acid Lipid Particle) - targeting KSP and VEGF in patients w liver mets

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.

• 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).

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

• Currently we have 44 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.
• In 2008 we accrued 210 patients in therapeutic studies.
• In 2009 we accrued 281 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.