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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: Gemcitabine
* Drug: Pertuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + gemcitabine<br>Participants 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). | Drug: Placebo<br>* Placebo was provided as a single-use formulation for infusion.<br>Drug: Gemcitabine<br>* Gemcitabine was provided as a solution for infusion.<br>* Other names: Gemzar;|
| Active Comparator: Pertuzumab + gemcitabine<br>Participants 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 | Drug: Gemcitabine<br>* Gemcitabine was provided as a solution for infusion.<br>* Other names: Gemzar;Drug: Pertuzumab<br>* Pertuzumab was provided as a single-use formulation for infusion.<br>* Other names: rhuMAb 2C4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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 | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Omnitarg, Cancer, Platinum-Resistant