A Phase 1b Study of AMG 386 in Combination With Either Pegylated Liposomal Doxorubicin or Topotecan in Subjects With Advanced Recurrent Epithelial Ovarian 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