A Study of Carboplatin and DOXIL Plus Bevacizumab in Patients With Platinum Sensitive Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancers

• The primary efficacy end point is the objective response rate to treatment defined as the proportion of patients with a Complete Response (CR) or Partial Response (PR) according to RECIST criteria from start of treatment to end ot treatment. [ Time Frame: Start of treatment until end of treatment ] [ Designated as safety issue: Yes ]
  

• The secondary efficacy endpoints include duration of response, progression-free survival (PFS) and time to disease progression (TTP) from the start of treatment (Cycle 1, Day 1) until the end of treatment. [ Time Frame: Progression Free Survival (interval between start of treatment Cycle 1, Day 1 until disease progression or death from any cause) and Time to Progression (interval between start of treatment until disease progression or death due to progression) ] [ Designated as safety issue: Yes ]
  

DOXIL pegylated liposomal doxorubicin (PLD) is approved for use in patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy. Data suggest that combination therapy of carboplatin plus DOXIL provides superior benefit to single agent therapy. Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is approved for use in combination with intravenous 5-fluorouracil-based chemotherapy for the treatment of metastatic colorectal cancer and in combination with carboplatin and paclitaxel (treatment of non-small cell lung cancer); and with paclitaxel (first line treatment of metastatic HER2-negative breast cancer). There are data showing bevacizumab has activity in the treatment of ovarian cancer, and it is currently being studied in platinum-sensitive relapsed ovarian cancer in combination with carboplatin/gemcitabine. No data exist on the efficacy and safety of bevacizumab administered with carboplatin and DOXIL. Based on the growing interest of incorporating bevacizumab in to ovarian cancer treatment and the activity seen to date, the evaluation of the combination of carboplatin and DOXIL with bevacizumab is warranted. This is a single arm (one dosing regimen), multicenter, open label (both the patient and the physician know what drug is being given) study in patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancers. This study will be conducted in multiple sites across the United States. All patients will receive DOXIL, carboplatin and bevacizumab by intravenous (IV) infusion for a maximum of ten (10) 28-day cycles. A disease response assessment will occur after the completion of Cycles 2, 4, 6, 8 and at the end of treatment. Patients will be followed for six (6) months post-treatment for progression-free survival. Disease progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST). RECIST is an accepted classification for response to treatment with classifications of Complete Response (CR), Partial Response( (PR), Progressive Disease (PD) or Stable Disease (SD).The primary objective of this study is to evaluate the objective response rate (Complete Response (CR) and Partial Response (PR)) to carboplatin and DOXIL treatment in combination with bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube and primary peritoneal cancers. The secondary objectives are to assess the safety profile of carboplatin and DOXIL in combination with bevacizumab as well as the following efficacy endpoints: Duration of response, Progression-free Survival, and Time to Progression. Safety will be evaluated using adverse events, clinical laboratory tests, and tests for cardiac function after the first 20 patients have been entered and received at least 2 cycles of therapy. Overall safety will be summarized at study completion. DOXIL (30 mg/m2), and carboplatin (area under the curve (AUC 5)) will be given on Day 1 of each 28-day cycle. Bevacizumab (10 mg/kg) will be given on days 1 and 15 of every 28-day cycle. All treatment will be given by intravenous (IV) infusion and repeated every 4 weeks for up to 10 cycles.