Experimental Therapies

The Cancer Pharmacology and Phase I Drug Development Group focuses primarily on the establishment of translational drug discovery into patients with all forms of cancer. The programs’ primary aim is to bring NEW AND NOVEL DRUG therapies to patients with all forms of cancer.

Specifically, two categories of studies have been established. One is clinical pharmacology (pharmacokinetic and pharmacodynamic) based studies. These studies explore the effect of food on oral drug disposition (e.g., effect of a standard meal on the pharmacokinetics of oral 9-nitrocamptothecin); drug-drug interaction studies that are clinically relevant (e.g., effect of CYP3A inhibitors on the pharmacokinetic disposition of an oral farnesyltransferase inhibitor, SCH66336) and basic clinical pharmacology of the disposition of novel single agent therapy (e.g., Phase I clinical trial of BMS-247550, a novel epothilone analog).

The other category is early phase I single agent and combination drug studies that are primarily focused on establishing toxicity profiles and the maximum tolerated dose of each agent when given alone or in combination (e.g., phase I trial of the combination of taxol with antisense oligonucleotides targeted against PKA RI"). The pharmacology laboratory is under development to support such clinical trials. However, present studies are being performed in collaboration with industry sponsors, CROs and the National Cancer Institute.  The objective of the phase I trial is to conduct comprehensive early clinical evaluation in all aspects of drug development including but not limited to PK-PD assessments, food-drug interaction studies, drug-drug interaction studies, population PK-PD analysis, oral compliance studies, and the ability to assess novel phase I trial designs as proposed in a recent review1.

At present, our phase I program conducts 12 active human studies with diverse array of agents including MBO against PKA RI alpha (GEM 231), farnesyltransferase inhibitors, 9-nitrocamptothecin (camptothecin analog), epothilone B analog (microtubule interactive agent), T607 (microtubule interactive agent), and oxaliplatin (DACH platinum agent). We plan on continued investigations into these and other novel agents. The total year to-date (1999-2002) accrual is projected annually to include 100 patients on all of these trials. The outcome of these studies will dictate the dose, schedules and tumor types to consider in moving novel agents further into phase II trials.

We have setup an infrastructure to evaluate these agents in phase II disease-specific clinical trials [e.g., L99-0025-phase II study of Rebecamycin Analogue NSC 655649 in Patients with Metastatic Colorectal Cancer (IMT Codes 23988, 23989, 23993)].

1Mani S, Gu Y, Wadler S, Fingert H. Antisense Therapeutics in Oncology: Points to Consider in Their Clinical Evaluation. Antisense & Nucleic Acid Drug Dev 1997, 9:543-547.

Dr. Sridhar Mani
(718) 904-2488
smani@montefiore.org

Sciode Oncology Associates 
(718) 881-1114 
fabio@sciode.com