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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
103
Liposomal doxorubicin 50 mg/m2 IV Q4W in combination with AMG 386 10 mg/kg IV QW
A3: AMG 386 15 mg/kg IV QW + Liposomal doxorubicin 50 mg/m2 IV Q4W
B1: AMG 386 10 mg/kg IV QW + Topotecan 4 mg/m2 IV days 1, 8, 15, of a 28 day dosing schedule
AMG 386 15mg/kg IV QW + Topotecan 4mg/m2 IV days 1, 8, 15 of a 28 day dosing schedule
Research Site
Tucson, Arizona, United States
Research Site
Sacramento, California, United States
Research Site
Orlando, Florida, United States
Research Site
Tampa, Florida, United States
Research Site
Saint Louis Park, Minnesota, United States
Research Site
Winston-Salem, North Carolina, United States
Research Site
Bismarck, North Dakota, United States
Research Site
Columbus, Ohio, United States
Research Site
Philadelphia, Pennsylvania, United States
Research Site
Adelaide, South Australia, Australia
...and 6 more locations
The primary objective is to identify the incidence of adverse events and clinical laboratory abnormalities defined as dose limiting toxicity in subjects treated with AMG 386 + pegylated liposomal doxorubicin (cohort A) and with AMG 386 + topotecan
Time frame: first 4 weeks of treatment
To evaluate the treatment effect as measured by: objective response rate (ORR), duration of response (DOR), PFS, change in tumor burden, CA 125 Response and Progression by GCIG and CA-125 duration of response
Time frame: Treatment and follow-up phase of study
To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs.
Time frame: first 4 weeks of treatment
To determine the pharmacokinetics of pegylated liposomal doxorubicin (and its metabolite, doxorubicinol), topotecan and AMG 386 (Cmax, AUC, and Cmin for intensive assessment; Cmax and Cmin for sparse assessment).
Time frame: Treatment and follow-up phase of study
To estimate the incidence of anti AMG 386 antibody formation.
Time frame: Treatment and follow-up phase of study
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