A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: A National Cancer Institute of Canada Clinical Trials Group Study

OBJECTIVE: BAY 12-9566 (tanomastat) is a biphenyl matrix metalloprotease inhibitor (MMPI) with antiangiogenic and antimetastatic properties in vivo. The objective of the study was to determine whether the addition of BAY 12-9566 after optimal response to chemotherapy could improve time to progression (TTP). PATIENTS AND METHODS: Patients enrolled in the study had received 6-9 cycles of platinum/paclitaxel containing chemotherapy for stage III or IV ovarian carcinoma, with a response of no evidence of disease, or complete or partial response with residual disease < 2 cm. Patients were then randomized to BAY 12-9566 800 mg p.o. b.i.d. or placebo. The primary endpoint was progression-free survival (PFS); secondary endpoints were quality of life, toxicity, changes in CA 125 levels, response, and overall survival (OS). The total planned sample size was 730. RESULTS: The study was closed after 243 patients had been randomized because of Bayer's decision to close all ongoing trials due to negative results from other phase III trials in pancreatic and small cell lung cancer. The final analysis was performed in August 2000 after the requisite number of events for the first planned interim analysis had occurred; 54% of patients had progressed and 18% had died. PATIENT CHARACTERISTICS: performance status was ECOG 0/1/2 in 65/33/2%; median age 57 years; 79% of patients were FIGO stage III; 41% were optimally debulked; 76% had serous histology, and 67% had > or = grade 3 histology. Toxicity was generally grade 1 or 2 in severity, with the most common (BAY 12-9566 vs. placebo) being nausea (26% vs. 13%), fatigue (24% vs. 12%), diarrhea (14% vs. 10%), rash (12% vs. 7%), grade 3/4 thrombocytopenia (3% vs. 1%), and grade 3/4 anemia (5% vs. 1%). Median time to progression (TTP) was 10.4 months (8.5-11.5) for BAY 12-9566 and 9.2 months (7.2-13.9) for placebo (P = 0.67). Median overall survival (OS) was 13.9 months (12.9-infinity) for BAY 12-9566 and 11.9 months (10.5-16.5) for placebo (P = 0.53). CONCLUSION: We conclude that BAY 12-9566 was generally well tolerated and at the time of the final analysis, there was no evidence of an impact of BAY 12-9566 on PFS or OS.