My goal is to develop independent clinical research skills allowing the organization of a self-sustained program in patient oriented research with a focus on novel agents. In order to participate in more than a cursory way in the translation of novel agents from the laboratory to the clinics, formal training in clinical trial methodology and selected basic sciences are required. In addition, real collaborative relationships with appropriate laboratory researchers must be established. Approximately 80 percent of patients with epithelial ovarian, fallopian tube, or peritoneal cancer will enter complete clinical remission following standard surgical cytoreduction and chemotherapy with a taxane and platinum containing regimen. The majority of patients will, however, relapse and opportunities to improve outcome exist by improving primary treatment, or in applying effective consolidation strategies following primary therapy.
Specific Aim 1 is to determine the efficacy of immune based consolidation therapy. Following completion of phase I/II studies, a phase III randomized trial between non-specific immune stimulation with KLH-QS21 conjugates and an antigen defined polyvalent vaccine developed at the center in conjunction with KLH-QS21 will be performed. This represents a definitive """"""""proof of principle"""""""" study, and time to treatment failure is the primary endpoint. Patients receiving non-specific immune stimulation will be able to cross over to vaccine at failure. Three-hundred total patients will be required.
Specific aim 2 is to determine the efficacy of systemically based consolidation approaches using agents with novel mechanisms of action (antiangiogenesis, for example), or new information regarding tumor biology (combined androgen blockade, for example). These studies will be applied to patients in second or greater complete clinical remission following relapse and chemotherapy to reinduce remission. A series of phase I/II trials are proposed: 1) Phase II study of bicalutamide/leuprolide, 2) Phase I/II study with Sugen-6668, 3)Phase I/II study with an endothelin receptor antagonist. The program is designed so that new strategies will be evaluated in the second or greater remission group of patients (Specific Aim 2) with a current median time to treatment failure of approximately 9-11 months. Promising strategies will be moved to patients in primary remission (Specific Aim 1) with a current median time to treatment failure of 18-21 months.
