Brief Title
AMG386 Comb w. Either Pegylated Liposomal Doxorubicin or Topotecan Subjects w. Advanced Recurrent Epithelial Ovarian CR
Official Title
A Phase 1b Study of AMG 386 in Combination With Either Pegylated Liposomal Doxorubicin or Topotecan in Subjects With Advanced Recurrent Epithelial Ovarian Cancer
Brief Summary
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.
Detailed Description
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
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
Secondary Outcome
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
Condition
Cancer
Intervention
A1: AMG 386 10 mg/kg + Liposomal doxorubicin
Study Arms / Comparison Groups
Part 1
Description: In part 1, six subjects will be assigned to each cohort A or B. This is a dose escalation/de escalation study with a 6 + 3 design based on the incidence of DLTs (dose limiting toxicities) during the first 4 weeks of combined therapy [(cohort A: AMG 386 and pegylated liposomal doxorubicin) or (cohort B: AMG 386 and topotecan)].
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
103
Start Date
January 2009
Completion Date
June 2015
Primary Completion Date
January 2012
Eligibility Criteria
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
MD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT00770536
Organization ID
20070182
Responsible Party
Sponsor
Study Sponsor
Amgen
Study Sponsor
MD, Study Director, Amgen
Verification Date
September 2015