Study of AMG 479 as Second Line Therapy in Patients With Recurrent Platinum-sensitive Ovarian Cancer

A Multicenter Open Label Phase II Study of the Efficacy and Safety of AMG 479, a Fully Human Monoclonal Antibody Against Insulin-like Growth Factor Type 1 Receptor (IGF-1R) as Second Line Therapy in Patients With Recurrent Platinum Sensitive Ovarian Cancer

The purpose of this study is to obtain an estimate of the objective response rate (ORR) of AMG 479 in patients with recurrent platinum-sensitive ovarian epithelial (including fallopian tube and primary peritoneal) carcinoma failing frontline chemotherapy.

Inclusion Criteria:

• Histologically-confirmed ovarian epithelial (including fallopian tube and primary peritoneal) carcinoma. Baseline paraffin embedded tissue from the patient's primary diagnosis is requested before study enrollment and should be forwarded to the designated central laboratory. In patients with measurable disease or sufficient ascites, fresh frozen tissue or ascites fluid should be obtained by needle biopsy and submitted to the designated central laboratory.
• Prior treatment with at most 1 treatment regimen in the primary treatment setting.
• Platinum-sensitive disease defined by recurrence or progression of disease > 6 months AND < 24 months after completion of prior platinum based chemotherapy.
• Female > 18 years of age or legal age.
• ECOG performance status ≤ 1.
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Subjects with non-measurable disease with a biochemical recurrence are eligible provided the CA 125 is elevated by more than 2 times the upper limits of normal, confirmed in two successive samples, drawn at least one week apart.
• Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE v.3.0 Grade ≤ 1 and to baseline laboratory values as defined in the inclusion criterion immediately below.
• Adequate organ and bone marrow function
• Nondiabetic patients or Type 1 or 2 Diabetic Patients controlled with HgbA1c < 8% and fasting blood glucose level <160 mg/dL
• Adequate coagulation parameters (within 21 days prior to registration), International Normalized Ratio (INR) ≤1.5; Activated ProThrombin Time (APTT) ≤ 1.5 x ULN.

Exclusion Criteria:

• More than 1 prior chemotherapy regimen in the treatment of ovarian cancer.
• Platinum-resistant disease as defined by a recurrence or progression less or equal to six months after completion of the frontline platinum based chemotherapy.
• Anticipation of a need for a major surgical procedure (e.g., impending bowel obstruction, gastrointestinal perforation) or radiation therapy during the trial.
• Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri.
• Prior treatment with investigational treatment targeted to IGF axis including, but not limited to, CP 751,871, IM-A12, RO4858696.
• Previous exposure to AMG 479.
• History of hypersensitivity to recombinant proteins.
• Prior treatment with a humanized monoclonal antibody.
• Treatment with chemotherapy, radiotherapy, surgery, blood products, or an investigational agent within 3 weeks of trial enrolment.
• Any of the following within 6 months prior to trial registration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.
• History of brain metastases, spinal cord compression, or carcinomatous meningitis.
• Patient of child-bearing potential is evidently pregnant (eg, positive human chorionic gonadotropin test) or is breast feeding.
• Patient of child-bearing potential is not willing to use adequate contraceptive precautions.
• Known active infection, or on antiretroviral therapy for HIV disease.
• Known positive test for chronic hepatitis B or C infection.
• Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the trial.
• Refusal or inability to give informed consent to participate in the trial.
• Other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the patient's safety, inhibit protocol participation, or interfere with interpretation of trial results, and in the judgment of the investigator would make the patient inappropriate for entry into this trial.