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