AMG386 Comb w. Either Pegylated Liposomal Doxorubicin or Topotecan Subjects w. Advanced Recurrent Epithelial Ovarian CR

September 25, 2015 updated by: Amgen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

103

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Research Site
    • Victoria
      • Footscray, Victoria, Australia, 3011
        • Research Site
      • Parkville, Victoria, Australia, 3050
        • Research Site
  • Belgium
      • Leuven, Belgium, 3000
        • Research Site
      • Liège, Belgium, 4000
        • Research Site
      • Liège, Belgium, 4000
        • Research Site
      • Wilrijk, Belgium, 2610
        • Research Site
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724-5024
        • Research Site
    • California
      • Sacramento, California, United States, 95817
        • Research Site
    • Florida
      • Orlando, Florida, United States, 32806
        • Research Site
      • Tampa, Florida, United States, 33612
        • Research Site
    • Minnesota
      • St. Louis Park, Minnesota, United States, 55426
        • Research Site
    • North Carolina
      • Winston Salem, North Carolina, United States, 27103
        • Research Site
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43219
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Part 1
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)].
Drug: A1: AMG 386 10 mg/kg + Liposomal doxorubicin
Liposomal doxorubicin 50 mg/m2 IV Q4W in combination with AMG 386 10 mg/kg IV QW
Other Names:
  • Liposomal doxorubicin
  • AMG 386
Drug: A3: AMG 386 15mg/kg + Liposomal doxorubicin
A3: AMG 386 15 mg/kg IV QW + Liposomal doxorubicin 50 mg/m2 IV Q4W
Other Names:
  • Liposomal doxorubicin
  • AMG 386
Drug: B1: AMG 386 10 mg/kg + Topotecan
B1: AMG 386 10 mg/kg IV QW + Topotecan 4 mg/m2 IV days 1, 8, 15, of a 28 day dosing schedule
Other Names:
  • Topotecan
  • AMG 386
Drug: B3: AMG 386 15mg/kg + Topotecan
AMG 386 15mg/kg IV QW + Topotecan 4mg/m2 IV days 1, 8, 15 of a 28 day dosing schedule
Other Names:
  • Topotecan
  • AMG 386
EXPERIMENTAL: Part 2
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
Drug: A1: AMG 386 10 mg/kg + Liposomal doxorubicin
Liposomal doxorubicin 50 mg/m2 IV Q4W in combination with AMG 386 10 mg/kg IV QW
Other Names:
  • Liposomal doxorubicin
  • AMG 386
Drug: A3: AMG 386 15mg/kg + Liposomal doxorubicin
A3: AMG 386 15 mg/kg IV QW + Liposomal doxorubicin 50 mg/m2 IV Q4W
Other Names:
  • Liposomal doxorubicin
  • AMG 386
Drug: B1: AMG 386 10 mg/kg + Topotecan
B1: AMG 386 10 mg/kg IV QW + Topotecan 4 mg/m2 IV days 1, 8, 15, of a 28 day dosing schedule
Other Names:
  • Topotecan
  • AMG 386
Drug: B3: AMG 386 15mg/kg + Topotecan
AMG 386 15mg/kg IV QW + Topotecan 4mg/m2 IV days 1, 8, 15 of a 28 day dosing schedule
Other Names:
  • Topotecan
  • AMG 386

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
first 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
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
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
Treatment and follow-up phase of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (ACTUAL)

January 1, 2012

Study Completion (ACTUAL)

June 1, 2015

Study Registration Dates

First Submitted

October 9, 2008

First Submitted That Met QC Criteria

October 9, 2008

First Posted (ESTIMATE)

October 10, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

September 29, 2015

Last Update Submitted That Met QC Criteria

September 25, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20070182

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoma

Clinical Trials on A1: AMG 386 10 mg/kg + Liposomal doxorubicin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe