Eligibility Criteria

Inclusion Criteria

Disease Related

• 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 are excluded

− Subjects with borderline ovarian cancer, ie, subjects with low malignant potential tumors, are excluded

− Subjects 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

• 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

• Radiologically evaluable disease per RECIST 1.1 with modifications

− There must be radiographically visible tumor

− Subjects with only ascites or pleural effusion are excluded

• 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.

− Subjects are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease.

Demographic

• Female 18 years of age or older at the time the written informed consent is obtained

• Subjects of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use an accepted and effective non-hormonal method of contraception [ie, double barrier method (eg, condom plus diaphragm)] from signing the informed consent through 6 months after last dose of study drug.

General

• GOG Performance Status of 0 or 1

• Life expectancy ≥ 3 months (per investigator opinion)

• Subject plans to begin protocol-directed therapy within 7 days from randomization

Laboratory

• Adequate organ and hematological function as evidenced by the following laboratory

studies prior to randomization:

− Hematological function, as follows:

63 Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

− PTT or aPTT ≤ 1.5 x ULN per institutional laboratory range and INR ≤ 1.5

− Renal function, as follows:

≤ 1+ on dipstick, unless quantitative protein is < 1000 mg in a

24-hour urine sample

calculated according to the Cockcroft-Gault formula

Exclusion Criteria

Disease Related

• 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 recurrence or progression during the first 6 cycles or < 6 months after the beginning of the first-line platinum-based chemotherapy are excluded

• 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

− If all sites of disease have been irradiated, documented progression must have occurred in at least 1 site of disease subsequent to the radiation therapy

• 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

Medications

• 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