Back to resultsAMG386 Comb w. Either Pegylated Liposomal Doxorubicin or Topotecan Subjects w. Advanced Recurrent Epithelial Ovarian CR
Primary Purpose
Cancer, Carcinoma, Fallopian Tube Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
A1: AMG 386 10 mg/kg + Liposomal doxorubicin
A3: AMG 386 15mg/kg + Liposomal doxorubicin
B1: AMG 386 10 mg/kg + Topotecan
B3: AMG 386 15mg/kg + Topotecan
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring fallopian tube cancer, Gynecological Malignancy, primary peritoneal cancer of predominantly epithelial origin, Stage II to IV ovarian cancer
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
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part 1
Part 2
Arm 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)].
The decision on declaration of a safe and tolerable dose during part 1 will lead to part 2 (cohort A: liposomal doxorubicin + AMG 386 MTD (max tolerated dose) of part 1, cohort B: Topotecan + AMG 386 MTD (max tolerated dose) of part 1
Outcomes
Primary Outcome Measures
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 Measures
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
To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs.
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).
To estimate the incidence of anti AMG 386 antibody formation.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00770536
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Carcinoma, Fallopian Tube Cancer, Gynecological Malignancies, Metastases, Oncology, Ovarian Cancer, Solid Tumors, Tumors
Keywords
fallopian tube cancer, Gynecological Malignancy, primary peritoneal cancer of predominantly epithelial origin, Stage II to IV ovarian cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
103 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1
Arm Type
Experimental
Arm 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)].
Arm Title
Part 2
Arm Type
Experimental
Arm Description
The decision on declaration of a safe and tolerable dose during part 1 will lead to part 2 (cohort A: liposomal doxorubicin + AMG 386 MTD (max tolerated dose) of part 1, cohort B: Topotecan + AMG 386 MTD (max tolerated dose) of part 1
Intervention Type
Drug
Intervention Name(s)
A1: AMG 386 10 mg/kg + Liposomal doxorubicin
Other Intervention Name(s)
Liposomal doxorubicin, AMG 386
Intervention Description
Liposomal doxorubicin 50 mg/m2 IV Q4W in combination with AMG 386 10 mg/kg IV QW
Intervention Type
Drug
Intervention Name(s)
A3: AMG 386 15mg/kg + Liposomal doxorubicin
Other Intervention Name(s)
AMG 386, Liposomal doxorubicin
Intervention Description
A3: AMG 386 15 mg/kg IV QW + Liposomal doxorubicin 50 mg/m2 IV Q4W
Intervention Type
Drug
Intervention Name(s)
B1: AMG 386 10 mg/kg + Topotecan
Other Intervention Name(s)
Topotecan, AMG 386
Intervention Description
B1: AMG 386 10 mg/kg IV QW + Topotecan 4 mg/m2 IV days 1, 8, 15, of a 28 day dosing schedule
Intervention Type
Drug
Intervention Name(s)
B3: AMG 386 15mg/kg + Topotecan
Other Intervention Name(s)
AMG 386, Topotecan
Intervention Description
AMG 386 15mg/kg IV QW + Topotecan 4mg/m2 IV days 1, 8, 15 of a 28 day dosing schedule
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs.
Time Frame
first 4 weeks of treatment
Title
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
Title
To estimate the incidence of anti AMG 386 antibody formation.
Time Frame
Treatment and follow-up phase of study
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724-5024
Country
United States
Facility Name
Research Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Research Site
City
St. Louis Park
State/Province
Minnesota
ZIP/Postal Code
55426
Country
United States
Facility Name
Research Site
City
Winston Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Research Site
City
Bismarck
State/Province
North Dakota
ZIP/Postal Code
58501
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43219
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Research Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Research Site
City
Footscray
State/Province
Victoria
ZIP/Postal Code
3011
Country
Australia
Facility Name
Research Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Research Site
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Research Site
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Research Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
AMG386 Comb w. Either Pegylated Liposomal Doxorubicin or Topotecan Subjects w. Advanced Recurrent Epithelial Ovarian CR
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