In. Criteria -Subjects must have histologically or cytologically documented epithelial ovarian (FIGO Stage II-IV), fallopian tube or primary peritoneal cancer.
(Subjects with pseudomyxoma or mesothelioma are excluded)
- Radiographically documented progression per RECIST criteria with modifications or progression of CA-125 as defined by the Rustin during or subsequent to the last chemotherapy regimen.
- May include measurable or non-measurable disease
- All scans and x-rays used to document measurable or non-measurable disease must be done within 3 weeks (21 days) of enrollment.
- No more than 3 previous regimens of anti-cancer therapy. Subjects must have received at least one platinum containing regimen
- 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 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.
Laboratory
- Adequate organ and hematological function as evidenced by the following laboratory studies within 2 weeks (14 days) of randomization:
- Hematological function, as follows:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L and ≤ 850 x 109/L Hemoglobin ≥ 9 g/dL PTT or aPTT≤ 1.5 x ULN per institutional laboratory rand and INR ≤ 1.5 x 109/L per instiutiona laboratory range
Renal function, as follows:
Creatinine ≤ 2.0 mg/dL Calculated creatinine clearance > 40 cc/min according to the Cockcroft-Gault formula
-Hepatic function, as follows: Total bilirubin ≤ 2.0 x ULN SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present) Nutritional
- Albumin ≥ 2.8 mg/dL General
- GOG Performance Status of 0 or 1
- Subject plans to begin protocol directed therapy within 7 days of randomization Ex Criteria
- Subjects believed to be a higher than average risk for bowel perforation. This includes symptoms of partial or complete bowel obstruction, recent (within 6 months) history of fistula or bowel perforation, subjects requiring total parenteral nutrition and continuous hydration
- Known ongoing small bowel dysfunction (ie, persistent nausea, vomiting)
- 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 one site of disease subsequent to the radiation therapy.
- Previous abdominal radiotherapy
- Has not yet completed a 21 day washout period for any previous anti-cancer systemic therapies (60 days for bevacizumab or any molecule of long half-life).
- Enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or is receiving other investigational agent(s)
- Current or prior history of central nervous system metastasis
- Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral neuropathy ≥grade 2
- History of arterial or venous thrombosis within 12 months prior to randomization
- Concurrent or prior (within 1 week before study day 1) anticoagulation therapy, excluding aspirin and anti platelet agents. The concurrent use of low molecular weight heparin or low dose warfarin (ie, ≤ 1 mg daily) for prophylaxis against thrombosis is acceptable while on study
- History of bleeding diathesis or clinically significant bleeding within 14 days of randomization
- Major surgical procedure within 4 weeks (28 days) prior to Study Day 1
- Minor surgical procedure, or placement of central venous access device, within 7 days of Study Day 1
- Paracentesis and/or thoracentesis are permitted prior to and while on study at the discretion of the investigator as clinically indicated. Investigators should document the frequency of paracenteses and/or thoracentesis that occurred prior to the enrollment of the subject in this study on the appropriate eCRFs. Investigators should also document each paracentesis and/or thoracentesis that occurs while a subject is on study on the appropriate eCRFs.
- Subjects with a history of prior malignancy, except:
- Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by treating physician
- Adequately treated non melanomatous skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prior myeloablative high dose chemotherapy with allogeneic or autologous stem cell (or bone marrow) transplant
- Clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
- Non-healing wound, ulcer or fracture
- Ongoing or active infection
- Unacceptable hypersensitivity to paclitaxel or drugs containing cremophor
- Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
- Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820
- Prior therapy against vascular endothelial growth factor or the vascular endothelial growth factor receptors including, but not limited to, bevacizumab, sunitinib, sorafenib, motesanib (AMG 706) or cediranib (AZD-2171), is permitted so long as the agent does not have any known activity against angiopoietin 1 or 2, or the receptors TIE-1 or TIE-2
- Current or within 30 days of randomization treatment with immune modulators such as cyclosporine and tacrolimus