2010 ONCY ASCO Abstract Posted - Ovarian
Not much in the early abstracts, all 3 trials were in early stages when the abstracts were submitted approx 5 months ago. This trial is a mono-therapy trial using both IP and IV delivery. It is also being run by the NCI
Phase I/II trial of reovirus serotype 3-Dearing strain in patients with recurrent ovarian cancer.
Sub-category: Ovarian Cancer
Category: Gynecologic Cancer
Meeting: 2010 ASCO Annual Meeting
Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr TPS253)
Abstract No: TPS253
Author(s): D. E. Cohn, G. Nuovo, M. C. Coffey, D. O'Malley, M. A. Villalona-Calero, M. R. Grever, D. Deam, J. A. Zwiebel, M. A. Phelps; Division of Gynecologic Oncology, The Ohio State University, Columbus, OH; The Ohio State University Medical Center, Columbus, OH; Oncolytics Biotech, Inc., Calgary, AB, Canada; Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD
Abstract:
Background: The prognosis associated with recurrent ovarian cancer is poor, and palliative therapy usually involves cytotoxic chemotherapy. In an effort to increase the survival and decrease the toxicity associated with treatment, increasing attention has been paid to targeted therapies. Reovirus Serotype 3-Dearing Strain (R) is a naturally occurring human reovirus. While reovirus infection is mild, R has been shown to replicate specifically in, and be cytopathic to, transformed cells possessing an activated Ras signaling pathway. In vivo, R has been demonstrated to be effective against solid tumors when administered into a tumor as well as intravenously (IV). In nude mice, intraperitoneal (IP) ovarian cancer cells are controlled with the administration of R. Given the improved survival with the use of IP chemotherapy in ovarian cancer, we set out to assess the feasibility and toxicity of the concurrent use of IV and IP R.
The trial was designed explicitly with correlative endpoints to establish the ability of IV and IP administered R to infect IP tumors and to assess the timing and method of reovirus infectivity in IP tumors.
Methods: Patients with recurrent ovarian cancer are eligible for this trial, and excluded if they had received more than one prior biologic agent for treatment of their disease. Patients are treated with a fixed dose of IV R days 1-5 (3 x 1010 TCID50/day) and an escalating dose of IP R days 1-2 (1 x 109 to 1011 TCID50/day) every 28 days.
The first cycle of therapy includes only IV treatment to provide the opportunity to assess the replication of R in IP tumors when the tumors are biopsied at the time of IP port placement; thereafter, each cycle includes both IV and IP administration of R. IP tumors are again biopsied before cycle 3, allowing for the assessment of replication of R after IV and IP administration. Samples of peritoneal fluid are obtained at the time of IP R for additional analysis.
A planned minimum of 18 patients will be treated on the phase I study, with an additional 27 on the phase II study utilizing the MTD (primary endpoint of the phase I study) of IP R (maximum 30+40=70); to date, 8 patients have been treated. The endpoint of the phase II study is the objective response rate, utilizing a 2-stage design.
