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

Ovarian Cancer Clinical Trial

Official title:

A Phase II, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy of Pertuzumab (rhuMAb 2C4) in Combination With Gemcitabine and the Effect of Tumor-Based HER2 Activation in Subjects With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00096993
• Other study ID #: TOC3258g
• Status: Completed
• Phase: Phase 2
• First received: November 17, 2004
• Last updated: June 8, 2015
• Start date: January 2005
• Est. completion date: September 2007

Study information

• Verified date: June 2015
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Peritoneal Cancer

Intervention

Drug:
• Placebo
Placebo was provided as a single-use formulation for infusion.
• Gemcitabine
Gemcitabine was provided as a solution for infusion.
• Pertuzumab
Pertuzumab was provided as a single-use formulation for infusion.

Locations

Country	Name	City	State
United States	Northern Virginia Pelvic Surgery Assoc.	Annandale	Virginia
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Alta Bates Comp. Cancer Ctr	Berkeley	California
United States	Univ. of Alabama at Birmingham	Birmingham	Alabama
United States	St. Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Center for Cancer and Hematologic Disease	Cherry Hill	New Jersey
United States	University Of Chicago	Chicago	Illinois
United States	North Idaho Cancer Center	Coeur d'Alene	Idaho
United States	Ohio State University College of Medicaine	Columbus	Ohio
United States	Pelvic Surgery Assoc.	Columbus	Ohio
United States	Corvallis Clinic	Corvallis	Oregon
United States	Wayne State Univ. Barbara Ann Karmanos Cancer Inst.	Detroit	Michigan
United States	California Cancer Crae, Inc	Greenbrae	California
United States	Comprehensive Cancer Institute	Huntsville	Alabama
United States	Indiana University	Indianapolis	Indiana
United States	St. Vincent Hospital	Indianapolis	Indiana
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Northwest Alabama Cancer Center	Muscle Shoals	Alabama
United States	Norwalk Medical Group	Norwalk	Connecticut
United States	Oklahoma Univ. Medical Center	Oklahoma City	Oklahoma
United States	Florida Hospital	Orlando	Florida
United States	Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Kaiser Permanente Northwest Division	Portland	Oregon
United States	Womens and Infants Hospital	Providence	Rhode Island
United States	Carilion Gyn/Onc	Roanoke	Virginia
United States	Sutter Cancer Center	Sacramento	California
United States	Sharp Healthcare	San Diego	California
United States	Southern California Permanente Medical Group (Kaiser)	San Diego	California
United States	Memorial Health Univ. Med. Ctr.	Savannah	Georgia
United States	Hematology Oncology, P.C.	Stamford	Connecticut
United States	Arizona Cancer Center	Tucson	Arizona
United States	Carle Clinic Association	Urbana	Illinois
United States	Cooper Health System	Voorhees	New Jersey
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	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.	Baseline to the end of the study (up to 1 year)	No
Secondary	Percentage of Participants With an Objective Response	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.	Baseline to the end of the study (up to 1 year)	No
Secondary	Duration of the Objective Response	Duration of the objective response was defined as the time from the initial response to disease progression or death from any cause.	Baseline to the end of the study (up to 1 year)	No
Secondary	Percentage of Participants Free From Disease Progression at 4 Months	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.	Baseline to Month 4	No
Secondary	Duration of Survival	Duration of survival was defined as the time from randomization until death from any cause.	Baseline to the end of the study (up to 1 year)	No