Fox Chase Cancer Center
MEDICAL ONCOLOGY: CLINICAL
TRIALS RESEARCH
LOUIS M. WEINER, M.D., Senior Member, Chairman, Medical
OncologyThe Department of Medical Oncology is responsible for the care of more than 3,500 new patients yearly. The research activities of the department represent a range of interests, including targeted cancer therapy, genetic events involved in cancer, and cellular resistance to chemotherapeutic agents, as well as fundamental research in the areas of breast, gastrointestinal, ovarian, prostate, and hematologic malignancies. These research efforts are discussed in detail in the individual reports from members of this department. In addition to fundamental and translationally-oriented laboratory research activities, clinical trials research is a fundamental priority of the department. With more than twenty active Phase I studies at any time, the Department of Medical Oncology continues to provide an important clinical trials outlet for novel translational concepts. Members of the department design and execute the majority of clinical trials supported by the Developmental Therapeutics Program, with a particular emphasis on innovative Phase I trials of new therapeutic agents or concepts. More than 175 patients were enrolled onto Phase I clinical trials in the past year.
CLINICAL TRIALS.The following are notable examples of the trials conducted by Medical Oncology members. A Phase I clinical trial was completed that employed perillyl alcohol (POH) in patients with refractory solid malignancies (HUDES). In this trial, the maximum tolerable dose (MTD) and optimum biological dose of POH were determined. The pharmacokinetics of POH and its major metabolites were also examined. Ras protein expression and the degree of inhibition of ras isoprenylation in lymphocytes and tumors of patients treated with POH were measured. The extent to which POH treatment results in decreased isoprenylation (geranyl-geranylation) of the GTP-binding proteins, RhoA and Rab4, in lymphocytes and tumors was also investigated. An ongoing Phase I clinical trial of the farnesyl transferase inhibitor R115777, an inhibitor of ras protein function is also being conducted (HUDES, WEINER). The aim of this trial is to determine the safety and pharmacokinetics of 21 day dosing of R115777. Phase I studies of combined anti-microtubule therapy employing taxanes and estramustine are also in progress (HUDES). The MTDs, as well as the toxic effects and pharmacokinetics, of these agents are under investigation. The binding of these agents to cytoskeletal proteins from tumor biopsies will also be determined.
Tumor vaccine studies include a Phase I trial of a viral canarypox vaccine into which the genes for the tumor antigen, carcino-embryonic antigen (CEA) and the immune co-stimulatory molecule B7.1 have been inserted (VON MEHREN). The safety, toxicities of immunization, and humoral response to the vaccine will be determined. And, importantly, the trial will show if immunization results in any signs of clinical activity. A vaccine employing the amino acid sequence encoded by the mutated ras oncogene in patients with pancreatic cancer is also under investigation (MEROPOL). The aims of this trial are to determine the toxicity, immunologic effects, and antitumor effects of ras peptide vaccine administration in patients with advanced pancreatic cancer.
The use of high-dose, pre-targeted radioimmunotherapy employing 90-Yttrium in patients with metastatic colorectal cancer was examined (WEINER). In addition, the appropriate doses of the active chemotherapy agents irinotecan and raltitrexed (tomudex) in patients with advanced gastrointestinal malignancies are being defined (MEROPOL). This trial is designed to determine the MTD and pharmacokinetics of irinotecan and tomudex administered in combination, to describe and quantify the toxicities associated with combined drug administration, and to document any antitumor activity of this two drug combination. The feasibility of sequential high dose therapy with autologous stem cell support in patients with ovarian cancer has been defined (SCHILDER). This trial aimed to determine the safety, feasibility, and toxicity of delivering dose-intense chemotherapy in previously untreated patients with advanced cancer. And, a tolerable and clinically active regimen of taxotere plus carboplatin was identified (LANGER); this regimen has potential applications in numerous malignancies. An innovative study employing SGN-10 (BR96 sFvPE40) is currently being conducted (BOOKMAN). SGN-10 is a recombinant immunotoxin targeting the BR96 (Lex) tumor antigen, which is overexpressed in diverse adenocarcinomas. The purpose of this trial is to evaluate the safety, MTD, and antitumor activity of SGN-10. The peak plasma concentration of SGN-10 and the development of anti-immunotoxin antibodies in patients will also be determined.
a P. Tsichlis: Present address-Kimmell Cancer Institute, Thomas Jefferson University, Philadelphia, PA, 19107
b R. Scher: Present address-Private Practice, Red Bank, NJ
c J. Sherley: Present address-Massachusetts Institute of Technology, Cambridge, MA, 02138
d S. Kindsfather: Present address-Private Practice, Trenton, NJ
e S. Johnson: Present address-University of Pennsylvania, Philadelphia, PA 19104
Illustrations or unpublished data in these reports should not be used without permission of the author.
| Fox Chase Cancer Center |
Scientific Report 1998 |