A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian Cancer

Inclusion criteria

• Signed informed consent
• Willingness to undergo tumor biopsy and disease that is amenable to biopsy (Cohort 1 only)
• Age >=18 years old
• Advanced, histologically documented carcinoma of the ovary
• Measurable disease with at least one lesion that can be accurately measured per RECIST in at least one dimension (longest dimension recorded). Each lesion must be >=20 mm when measured by conventional techniques, including palpation, plain X-ray, CT, and MRI, or >=10 mm when measured by spiral CT.
• Or, clinically or radiologically detectable disease (e.g., ascites, peritoneal deposits, mesenteric thickening or lesions that do not fulfill RECIST for measurable disease). In addition, the subject must have two consecutive pre-treatment CA 125 levels that are both greater than 2× the institutional upper limit of normal (ULN) and >=40 IU/mL, taken at least 1 week and not more than 3 months apart. The second of the two measurements of CA 125 level should not be drawn within 28 days following the screening biopsy. The later value must be within 2 weeks of starting rhuMAb 2C4 treatment.
• One or more prior platinum-based chemotherapeutic regimens for the management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound
• Life expectancy >=12 weeks
• ECOG performance status 0 or 1
• Use of an effective means of contraception (for women of childbearing potential)
• Granulocyte count >=1500/uL, platelet count of >=75,000/uL, and hemoglobin >=9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbopoeitin [Aranesp] is permitted)
• Serum bilirubin <=1.5× the ULN and alkaline phosphatase, AST, and ALT <=2.5× ULN (ALT, AST, and alkaline phosphatase <=5× ULN for subjects with liver metastases)
• Serum creatinine <=1.5× ULN
• International normalized ratio (INR) <1.5 and activated partial thromboplastin time (aPTT) <1.5 ULN (except for subjects receiving warfarin)

Exclusion criteria

• Prior treatment with experimental anti-cancer agents within 4 weeks prior to Day 1 (the day on which the first rhuMAb 2C4 infusion is administered)
• Prior treatment with HER pathway inhibitors (e.g., Herceptin [Trastuzumab], Iressa [gefitinib], Tarceva [erlotinib hydrochloride], C225, CI1033, and TAK165)
• History or clinical evidence of central nervous system or brain metastases
• Ejection fraction, determined by ECHO, <50%
• Uncontrolled hypercalcemia (>11.5 mg/dL)
• Prior exposure to doxorubicin or liposomal doxorubicin >360 mg/m2 , mitoxantrone >120 mg/m2 , or idarubicin >90 mg/m2
• History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or basal or squamous cell skin cancer
• History of serious systemic disease, including active infection, uncontrolled hypertension (diastolic blood pressure >100 mmHg on two consecutive occasions), unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible)
• Ongoing liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus infection
• Pregnancy or lactation
• Major surgery or significant traumatic injury within 3 weeks prior to Day 1 with the exception of tumor biopsy for the purposes of the study
• 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