A Phase 3, Randomized, Double-Blind Trial of Weekly Paclitaxel Plus AMG 386 or Placebo in Women With Recurrent Partially Platinum Sensitive or Resistant Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers
Inclusion Criteria:
- Female 18 years of age or older at the time the written informed consent is obtained
- Gynecologic Oncology Group (GOG) Performance Status of 0 or 1
- Life expectancy >= 3 months (per investigator opinion)
- Histologically or cytologically documented invasive epithelial ovarian cancer,
primary peritoneal cancer, or fallopian tube cancer (Subjects with pseudomyxoma ,
mesothelioma, unknown primary tumor, sarcoma, or neuroendocrine histology, with
borderline ovarian cancer, ie, subjects with low malignant potential tumors, and with
clear cell or mucinous histology are excluded)
- Subjects must have undergone surgery for ovarian cancer, primary peritoneal cancer,
or fallopian tube cancer including at least a unilateral oophorectomy
- Radiologically evaluable disease per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 with modifications
- Subjects must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease containing carboplatin, cisplatin, or another
organoplatinum compound. This initial treatment may have included intraperitoneal
therapy, high-dose therapy, consolidation therapy, bevacizumab or extended therapy
administered after surgical or non-surgical assessment.
- Adequate organ and hematological function
- Generally well controlled blood pressure with systolic blood pressure <= 140 mmHg and
diastolic blood pressure <= 90 mmHg prior to randomization. The use of
anti-hypertensive medications to control hypertension is permitted
- Radiographically documented disease progression either on or following the last dose
of prior chemotherapy regimen for epithelial ovarian cancer, primary peritoneal
cancer, or fallopian tube cancer
Exclusion Criteria:
- Subjects who have received more than 3 previous regimens of anti-cancer therapy for
epithelial ovarian, primary peritoneal or fallopian tube cancers
- Subjects who have received paclitaxel as consolidation therapy, maintenance, or
monotherapy are excluded
- Subjects with primary platinum-refractory disease
- Subjects with platinum-free interval (PFI) > 12 months from their last platinum based
therapy
- Radiotherapy <= 14 days prior to randomization. Subjects must have recovered from
all radiotherapy-related toxicities
- Previous abdominal or pelvic radiotherapy
- History of arterial or venous thromboembolism within 12 months prior to randomization
- History of clinically significant bleeding within 6 months prior to randomization
- History of central nervous system metastasis
- Has not yet completed a 21 day washout period prior to randomization for any previous
anti cancer systemic therapies (30 days for prior bevacizumab)
- Enrolled in or has not yet completed at least 30 days (prior to randomization) since
ending other investigational device or drug, or currently receiving other
investigational treatments
- Unresolved toxicities from prior systemic therapy that are Common Terminology
Criteria for Adverse Events (CTCAE) Version 3.0 >= Grade 2 in severity except
alopecia
- Known active or ongoing infection (except uncomplicated urinary tract infection
[UTI]) within 14 days prior to randomization
- Currently or previously treated with AMG 386, or other molecules that inhibit the
angiopoietins or Tie2 receptor
- Treatment within 30 days prior to randomization with strong immune modulators
including but not limited to systemic cyclosporine, tacrolimus, sirolimus,
mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, and
lenalidomide
- Clinically significant cardiovascular disease within 12 months prior to randomization
- Major surgery within 28 days prior to randomization or still recovering from prior
surgery
- Minor surgical procedures, except placement of tunneled central venous access device
within 3 days prior to randomization. Diagnostic laparoscopy is regarded as a minor
surgical procedure.