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

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

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.

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