Trial Information

A Phase II Single Arm Study of Carboplatin and DOXIL (PLD) Plus Bevacizumab in Patients With Platinum Sensitive Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancers

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.