A phase II study evaluating Avastin in combination with Zybrestat demonstrated increased progression-free survival in recurrent ovarian cancer.
The study, known as Gynecologic Oncology Group protocol 186I, met its primary endpoint of a statistically significant increase in progression-free survival (p < 0.05; HR=0.685) for the combination compared to Avastin alone.
The study is the first and currently only randomized trial to test an antiangiogenic therapeutic agent combined with a vascular disrupting agent, without including any cytotoxic chemotherapy.
The trial enrolled 107 patients with platinum-sensitive and -resistant recurrent ovarian cancer at 67 clinical sites in the U.S.
Patients were randomized 1:1 into one of two treatment arms: one arm received Avastin (bevacizumab), and the second arm received Avastin plus Zybrestat (fosbretabulin; CA4P). Both therapies were administered intravenously every three weeks and patients were treated until disease progression or until adverse effects prohibited further therapy. Secondary endpoints in the study include safety, objective response rate according to RECIST criteria, and overall survival.
Patients receiving the combination of Zybrestat and Avastin achieved a higher objective response rate, which was not statistically significant. All patients will continue to be followed for overall survival.
Consistent with prior clinical experience with Zybrestat, patients in the combination arm experienced a higher incidence of hypertension compared to the control arm. All cases of hypertension were managed with antihypertensive treatments, as specified in the study protocol.
For this study, Zybrestat is provided to CTEP under a Cooperative Research and Development Agreement with OXiGENE Inc., and bevacizumab is being provided as an investigational agent under a CRADA with Genentech. Bevacizumab is not approved to treat women with ovarian cancer in the U.S.; however, it is approved in other countries for treatment of ovarian cancer.
Zybrestat exerts its antitumor effects through the validated therapeutic mechanism of tumor blood supply deprivation. By selectively affecting and disabling tumor vasculature, Zybrestat reduces the blood supply necessary for tumor growth and survival.
