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A Study to Evaluate rhuMab 2C4 and Gemcitabine in Subjects With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Phase 2
Completed
Conditions
Peritoneal Cancer
Fallopian Tube Cancer
Ovarian Cancer
Interventions
Registration Number
NCT00096993
Lead Sponsor
Genentech, Inc.
Brief Summary

This is a Phase II, randomized, placebo-controlled, double-blind, multicenter clinical trial of pertuzumab in combination with gemcitabine relative to placebo in combination with gemcitabine in subjects with advanced ovarian, primary peritoneal, or fallopian tube cancer that is resistant to platinum-based chemotherapy.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
131
Inclusion Criteria
  • Signed informed consent
  • Age >= 18 years
  • Advanced, histologically documented ovarian, primary peritoneal, or fallopian tube carcinoma
  • Representative tumor specimens in paraffin blocks or at least 12 unstained slides with an associated pathology report, obtained at any time prior to entry of study for evaluation of HER2 activation
  • Measurable disease with at least one lesion that can be accurately measured in at least one dimension (longest dimension recorded), Or:
  • Clinically or radiologically detectable disease (e.g., ascites, peritoneal deposits, mesenteric thickening or lesions that do not fulfill RECIST for measurable disease)
  • Platinum-resistant or refractory carcinoma
  • Life expectancy >= 12 weeks
  • ECOG performance status 0 or 1
  • LVEF >= 50%, as determined by ECHO
  • Use of an effective means of contraception (for women of childbearing potential)
  • Clinical laboratory test results: Granulocyte count >= 1500/uL; Platelet count >= 75,000/uL; Hemoglobin >= 9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbopoeitin [Aranesp(R)] is permitted); Serum bilirubin <= 1.5 the ULN; Alkaline phosphatase, AST, and ALT <= 2.5 ULN (AST, ALT <= 5 ULN for subjects with liver metastasis); Serum creatinine <= 1.5 ULN; International normalized ratio (INR) <= 1.5 and activated partial thromboplastin time (aPTT) <= 1.5 ULN (except for subjects receiving anti-coagulation therapy)
Exclusion Criteria
  • Prior treatment with gemcitabine
  • Two or more prior regimens for the treatment of platinum-resistant disease
  • Two or more non-platinum-containing regimens for the treatment of platinum-sensitive disease
  • Prior treatment with experimental anti-cancer agents within 4 weeks prior to Day 1 (the day the first study treatment infusions are administered)
  • Prior treatment with HER2 pathway inhibitors (e.g., Herceptin(R) [trastuzumab], Iressa(R) [gefitinib], Tarceva<TM> [erlotinib hydrochloride], cetuximab, GW572016)
  • History or clinical evidence of central nervous system or brain metastases
  • Uncontrolled hypercalcemia ( > 11.5 mg/dL)
  • Prior exposure of > 360 mg/m^2 doxorubicin or liposomal doxorubicin, > 120 mg/m^2 mitoxantrone, or > 90 mg/m^2 idarubicin
  • History of other malignancies within 5 years of Day 1, except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of breast, basal or squamous cell skin cancer
  • History of serious systemic disease, unstable angina, myocardial infarction within 6 months prior to Day 1 of treatment, symptoms of CHF, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia [i.e., atrial fibrillation, paroxysmal supraventricular tachycardia] are eligible)
  • Known HIV infection
  • Pregnancy or lactation
  • Major surgery or significant traumatic injury within 3 weeks prior to Day 1 of treatment
  • Inability to comply with study and follow-up procedures
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + gemcitabinePlaceboParticipants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles).
Placebo + gemcitabineGemcitabineParticipants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles).
Pertuzumab + gemcitabinePertuzumabParticipants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles
Pertuzumab + gemcitabineGemcitabineParticipants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles
Primary Outcome Measures
NameTimeMethod
Progression-free SurvivalBaseline to the end of the study (up to 1 year)

Progression-free survival was defined as the time from the first day of treatment (Cycle 1, Day 1) to the time of documented disease progression or death, whichever occurred first. Disease progression was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) was defined as \>=30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With an Objective ResponseBaseline to the end of the study (up to 1 year)

An objective response was defined as a complete or partial response determined on two consecutive occasions ≥ 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors (RECIST). A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.

Duration of the Objective ResponseBaseline to the end of the study (up to 1 year)

Duration of the objective response was defined as the time from the initial response to disease progression or death from any cause.

Percentage of Participants Free From Disease Progression at 4 MonthsBaseline to Month 4

Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.

Duration of SurvivalBaseline to the end of the study (up to 1 year)

Duration of survival was defined as the time from randomization until death from any cause.

Trial Locations

Locations (41)

Carle Clinic Association

🇺🇸

Urbana, Illinois, United States

Franklin Square Hospital Center

🇺🇸

Baltimore, Maryland, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Pelvic Surgery Assoc.

🇺🇸

Columbus, Ohio, United States

Comprehensive Cancer Institute

🇺🇸

Huntsville, Alabama, United States

Ventura County Hematology Oncology Specialists

🇺🇸

Oxnard, California, United States

Integrated Community Oncology Network

🇺🇸

Jacksonville, Florida, United States

Florida Hospital

🇺🇸

Orlando, Florida, United States

Greater Baltimore Medical Center

🇺🇸

Baltimore, Maryland, United States

Oklahoma Univ. Medical Center

🇺🇸

Oklahoma City, Oklahoma, United States

Womens and Infants Hospital

🇺🇸

Providence, Rhode Island, United States

Carilion Gyn/Onc

🇺🇸

Roanoke, Virginia, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Cooper Health System

🇺🇸

Voorhees, New Jersey, United States

Kaiser Permanente Northwest Division

🇺🇸

Portland, Oregon, United States

Center for Cancer and Hematologic Disease

🇺🇸

Cherry Hill, New Jersey, United States

Corvallis Clinic

🇺🇸

Corvallis, Oregon, United States

Hematology Oncology, P.C.

🇺🇸

Stamford, Connecticut, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

North Idaho Cancer Center

🇺🇸

Coeur d'Alene, Idaho, United States

Norwalk Medical Group

🇺🇸

Norwalk, Connecticut, United States

Northwest Alabama Cancer Center

🇺🇸

Muscle Shoals, Alabama, United States

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Univ. of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

Alta Bates Comp. Cancer Ctr

🇺🇸

Berkeley, California, United States

Cancer Center of Kansas

🇺🇸

Wichita, Kansas, United States

Memorial Health Univ. Med. Ctr.

🇺🇸

Savannah, Georgia, United States

St. Vincent Hospital

🇺🇸

Indianapolis, Indiana, United States

Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

Northern Virginia Pelvic Surgery Assoc.

🇺🇸

Annandale, Virginia, United States

Ohio State University College of Medicaine

🇺🇸

Columbus, Ohio, United States

California Cancer Crae, Inc

🇺🇸

Greenbrae, California, United States

Sutter Cancer Center

🇺🇸

Sacramento, California, United States

Southern California Permanente Medical Group (Kaiser)

🇺🇸

San Diego, California, United States

University of California, Los Angeles

🇺🇸

Los Angeles, California, United States

University Of Chicago

🇺🇸

Chicago, Illinois, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

St. Luke's Mountain States Tumor Institute

🇺🇸

Boise, Idaho, United States

Wayne State Univ. Barbara Ann Karmanos Cancer Inst.

🇺🇸

Detroit, Michigan, United States

Sharp Healthcare

🇺🇸

San Diego, California, United States

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