This study is a 2 part, 2 cohort, open-label, dose escalation/de escalation study of AMG 386 in combination with either pegylated liposomal doxorubicin or topotecan in subjects with recurrent ovarian cancer. Up to 100 subjects will be enrolled to receive AMG 386 in combination with either pegylated liposomal doxorubicin every 4 weeks (cohort A) or topotecan weekly on days 1, 8, and 15 of a 28 day dosing schedule (cohort B). Subject enrollment and assignment to either cohort will be based on eligibility and the investigator's discretion.

It is hypothesized that AMG 386, in combination with each of the chemotherapy regimens: either pegylated liposomal doxorubicin or topotecan will be safe and well tolerated in subjects with recurrent ovarian cancer.

The purpose of this study is to evaluate the effectiveness and safety of AMG 386 when used with pegylated liposomal doxorubicin or topotecan in subjects with advanced recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer

Inclusion Criteria:

• Histologically or cytologically documented recurrent invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer
• Subjects must have received at least one platinum containing regimen
• Radiographically documented progression per RECIST criteria with modifications or progression of CA 125 as adopted by GCIG during or subsequent to the last chemotherapy regimen
• Subjects may include those with measurable or non measurable disease
• All scans and x-rays used to document measurable or non measurable disease must be done within 28 days prior to enrollment
• Female 18 years of age or older at the time the written informed consent is obtained
• GOG Performance Status of 0 or 1
• Left Ventricular Ejection Fraction (LVEF) >= institutional lower limit of normal for subjects assigned to cohort A only
• Adequate organ function as assessed by laboratory studies (hematological and chemistries)
• Life expectancy >= 3 months (per investigator opinion)
• 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 double barrier non hormonal method of contraception from signing the informed consent through 6 months after last dose of study drug

Exclusion Criteria:

• Subjects believed to be a higher than average risk of 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

• Previous abdominal /or pelvic external beam radiotherapy

• Known history of central nervous system metastases

• Subjects with a history of prior malignancy, except:

  • Malignancy treated with curative intent and with no known active disease present for >= 3 years before study day 1 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

• History of arterial or deep venous thromboembolism within 12 months prior to enrollment

• Clinically significant cardiac disease within 12 months prior to enrollment

• Prior treatment with doxorubicin or pegylated liposomal doxorubicin (cohort A subjects) and topotecan (cohort B subjects)

• Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine and tacrolimus