Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With Ovarian Cancer

October 13, 2015 updated by: Amgen

A Phase 1b Open-Label, Multi-Center Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With High-Risk Stage I and Stages II-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers

To evaluate whether AMG 386 in combination with paclitaxel and carboplatin is safe and well tolerated in the first-line treatment of high-risk stage I and stages II-IV epithelial ovarian, primary peritoneal and fallopian tube cancers. The hypothesis is that AMG 386 in combination with carboplatin and paclitaxel is safe and well tolerated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

To evaluate whether AMG 386 in combination with paclitaxel and carboplatin is safe and well tolerated in the first-line treatment of high-risk stage I and stages II-IV epithelial ovarian, primary peritoneal and fallopian tube cancers. The hypothesis is that AMG 386 in combination with carboplatin and paclitaxel is safe and well tolerated.

Study Type

Interventional

Enrollment (Actual)

27

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
    • Victoria
      • Footscray, Victoria, Australia, 3011
        • Research Site
      • Malvern, Victoria, Australia, 3144
        • Research Site
      • Parkville, Victoria, Australia, 3052
        • Research Site
  • Belgium
      • Brussels, Belgium, 1000
        • Research Site
      • Bruxelles, Belgium, 1200
        • Research Site
      • Leuven, Belgium, 3000
        • Research Site
  • Spain
      • Madrid, Spain, 28040
        • Research Site
    • Cataluña
      • Barcelona, Cataluña, Spain, 08035
        • 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:

  • Female subjects more than 18 years of age with newly diagnosed high-risk FIGO Stage I (grade 3, or aneuploid grade 1 or 2) or Stages II-IV epithelial ovarian, primary peritoneal and fallopian tube cancer with an indication for first-line treatment with paclitaxel and carboplatin x 6 cycles. Subjects with pseudomyxoma, mesothelioma, adenocarcinoma of unknown primary tumor, sarcoma, or neuroendocrine histology are excluded.
  • Subjects with high-risk stage I, stage II, or stage IIIA-B must have had prior primary debulking surgery that occurred no less than 4 weeks, and no more than 12 weeks, prior to enrollment. Subjects must have recovered fully from surgery in the opinion of the investigator
  • Subjects with Stage IIIC or IV disease who have not had primary debulking surgery must have planned interval debulking surgery following 3 cycles of AMG 386, paclitaxel and carboplatin
  • Female 18 years of age or older at the time the written informed consent is obtained
  • 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 non-hormonal method of contraception (i.e, double barrier method (eg, condom plus diaphragm) from signing the informed consent through 6 months after last dose of study drug
  • GOG Performance Status of 0 or 1
  • Life expectancy ≥ 3 months (per investigator opinion)
  • Subject plans to begin protocol-directed therapy within 7 days from enrollment
  • Adequate organ and hematological function as evidenced by the following laboratory studies prior to enrollment:

Hematological function, as follows:

  • Hemoglobin ≥ 9 g/dL
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10x9/L
  • Platelet count ≥ 100 x 10x9/L and ≤ 850 x 10x9/L
  • PTT or aPTT ≤ 1.5 x ULN per institutional laboratory range and INR ≤ 1.5

Renal function, as follows:

  • Urinary protein quantitative value of ≤ 30 mg/dL in urinalysis or ≤ 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample
  • Creatinine clearance > 40 mL/min per 24-hr urine collection or calculated according to the Cockcroft-Gault formula

Hepatic function, as follows:

  • AST and ALT ≤ 2.5 x ULN per institutional laboratory range (or ≤ 5 x ULN if liver metastases are present)
  • Total bilirubin ≤ 1.5x institutions' ULN Nutritional
  • Albumin ≥ 2.8 g/dL

Exclusion Criteria:

  • Prior use of anticancer therapy or experimental therapy for epithelial ovarian, primary peritoneal or fallopian tube cancers
  • Previous abdominal and/or pelvic external beam radiotherapy
  • Subjects believed to be a higher than average risk of bowel perforation. This includes current 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
  • History of arterial or venous thromboembolism within 12 months prior to enrollment
  • History of clinically significant bleeding within 6 months prior to enrollment
  • History of central nervous system metastasis
  • Known active or ongoing infection (except uncomplicated urinary tract infection) within 14 days prior to enrollment
  • Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
  • Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine or tacrolimus
  • Prior myeloablative high-dose chemotherapy with allogeneic or autologous stem cell (or bone marrow) transplant
  • Clinically significant cardiac disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent
  • Uncontrolled hypertension as defined as diastolic blood pressure > 90 mmHg OR systolic blood pressure > 140 mmHg. The use of anti-hypertensive medications to control hypertension is permitted
  • Subjects with a history of prior malignancy, except:

Malignancy treated with curative intent and with no known active disease present for ≥ 3 years prior to enrollment 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

  • Major surgery within 28 days prior to enrollment or still recovering from prior surgery
  • Minor surgical procedures, including placement of tunneled central venous access device, within 3 days prior to enrollment
  • History of allergic reactions to bacterially-produced proteins
  • Hypersensitivity to paclitaxel or drugs using the vehicle cremophor
  • Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding or planning to become pregnant within 6 months after the end of treatment
  • Subject has known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection
  • Any condition which in the investigator's opinion makes the subject unsuitable for study participation
  • Any uncontrolled concurrent illness or history of any medical condition that may interfere with the interpretation of the study results
  • Non-healing wound, ulcer (including gastrointestinal) or fracture
  • Subject has previously been enrolled onto this study
  • Subject will not be available for follow-up assessment
  • Subject has known sensitivity to any of the products to be administered during dosing
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AMG 386, paclitaxel and carboplatin
15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months.
Drug: AMG 386, paclitaxel and carboplatin
15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To evaluate whether AMG 386 in combination with paclitaxel and carboplatin is safe and well tolerated in the first-line treatment of high-risk stage I and stages II-IV epithelial ovarian, primary peritoneal and fallopian tube cancers.
Time Frame: 18 weeks of combination therapy
18 weeks of combination therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate the pharmacokinetics (Cmax, AUC and Cmin) of AMG 386 in combination with carboplatin and paclitaxel
Time Frame: Week 1 until Week 7
Week 1 until Week 7
To estimate the incidence of anti-AMG 386 antibody formation
Time Frame: Week 1 until maximum of 1 year following first dose
Week 1 until maximum of 1 year following first dose
To evaluate the objective response rate (ORR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
Time Frame: From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.
From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.
To evaluate the duration of response (DOR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
Time Frame: From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.
From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.
To evaluate progression-free survival (PFS) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
Time Frame: From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.
From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.
To evaluate the number of participants with adverse events and clinical laboratory abnormalities
Time Frame: 96 weeks
96 weeks
To evaluate the effect of AMG 386 on the pharmacokinetics (Cmax, AUC and Cmin) of carboplatin and paclitaxel
Time Frame: Week 1 until Week 7
Week 1 until Week 7

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.

General Publications

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

November 1, 2010

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

October 21, 2010

First Submitted That Met QC Criteria

December 2, 2010

First Posted (Estimate)

December 3, 2010

Study Record Updates

Last Update Posted (Estimate)

October 14, 2015

Last Update Submitted That Met QC Criteria

October 13, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20090155

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.

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