Eric H. Rubin, MD, Director of Investigational Therapeutics, The Cancer Institute of New Jersey, professor of medicine, UMDNJ-Robert Wood Johnson Medical School

As director of the Phase I Clinical Trials Team at The Cancer Institute of New Jersey (CINJ), I evaluate promising new drugs in the treatment of patients with cancer. The Clinical Trials Team includes doctors, nurses, pharmacologists, and trial coordinators who specialize in conducting clinical phase I and pharmacologic trials involving cancer patients. This resource is particularly important in New Jersey, which has one of the highest cancer incidence rates in the country. CINJ is the only National Cancer Institute-designated Comprehensive Cancer Center in the state.

Our team works with both CINJ investigators and pharmaceutical companies to design and implement phase I trials of promising new drugs. These partnerships are with many pharmaceutical companies including: Merck & Co., Inc., Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Novartis, and Pfizer, to name a few. We also provide preclinical services for trial development, including evaluation of new drugs in cell culture and animal models of cancer. These services are provided in part by our Pharmacokinetics/Pharmacodynamics Shared Resource. This resource includes state-of-the-art HPLC and mass spectrometry equipment, and assists investigators in developing blood and tissue sampling strategies, as well as GLP-based analytical methods for assaying drug concentrations.

Phase I trials involving cancer patients are challenging for several reasons. The patients are often ill, yet the trials require frequent visits to the clinic for pharmacokinetic or safety evaluations. In the current era of targeted therapeutics, biopsies of skin or a cancer site are often necessary to determine whether a new drug is effectively modulating its target. Our trials typically include a variety of biomarker studies, such as evaluation of genetic polymorphisms, assessment of target protein levels and modifications, and transcriptional profiling using microarrays. Having an experienced and compassionate nursing and technical staff is therefore critical in ensuring that the highest quality patient care is maintained in conjunction with completion of the trial endpoints. At CINJ, this staff includes experienced advanced practice nurses.

Since its inception in 1995, our Phase I Clinical Trials Team has completed 26 trials, including 12 trials that were investigator-initiated, with six of these funded by the National Cancer Institute. Several of the trials were first-in-human studies, and involved drugs that were ultimately approved by the FDA for the treatment of cancer, including cetuximab and gefitinib. Our currently open phase I trials involve a variety of promising new strategies for the treatment of cancer, including inhibition of aurora kinase, histone deacetylases, kinesin spindle protein, and mTOR. We are also testing strategies developed by CINJ investigators, including vaccines for bladder cancer, donor lymphocyte infusions for lymphoma and kidney cancers, phorbol ester for leukemia, intraperitoneal delivery of new anti-folate drugs for gastrointestinal cancers and selenium for the prevention of drug resistance in ovarian cancer.

Among our currently open phase I trials, particularly promising results have been observed in a study of the combination of gemcitabine and imatinib mesylate (Gleevec), led by Elizabeth Poplin, MD. This study was based on preclinical work suggesting that imatinib mesylate would enhance the accumulation of gemcitabine at sites of cancer metastasis. To date, evidence of significant anti-cancer activity as assessed by serum tumor markers has been observed in six of seven patients with pancreatic cancer who were enrolled in this trial. These promising results have stimulated phase II trials for this drug combination in patients with pancreatic cancer.