A Randomized, Double-blind, Placebo Controlled, Multi-center, Phase II Study of Adding AMG 479, a Fully Human Monoclonal Antibody Against Insulin-like Growth Factor Type 1 Receptor (IGF-1R) to First Line Chemotherapy in Patients With Optimally Debulked ( < 1 cm ) Epithelial Ovarian Cancer
- Histologically-confirmed optimally debulked (< 1 cm) FIGO stage III or stage IV
(positive pleural cytology only) ovarian epithelial (including fallopian tube and
primary peritoneal) carcinoma.
- Patients should have undergone surgical debulking, by a surgeon experienced in the
management of ovarian cancer, with the aim of maximal surgical cytoreduction. All
patients must be optimally debulked as defined as having no residual tumor of greater
than 1 cm in the post surgical setting.
- Patients with stage IV disease will be eligible if a positive pleural cytology is the
only extra peritoneal disease.
- Paraffin block (or 10 - 20 unstained slides) and fresh frozen surgical/biopsy
specimens of the primary tumor are required at baseline.
- No prior systemic treatment in the primary disease treatment setting.
- Female > 18 years of age or legal age.
- ECOG performance status ≤ 2.
- Adequate organ and bone marrow function
- Non diabetic patients or Type 1 or 2 Diabetic Patients:
• Diabetes must be controlled with HgbA1c < 8% and fasting blood glucose level <160
- Patient must be willing and able to comply with scheduled visits, and all study
- Informed consent obtained.
- Patients should be able to commence systemic therapy within 6 weeks of cytoreductive
- Life expectancy > 12 weeks.
- Adequate coagulation parameters (within 14 days prior to randomization),
International Normalized Ratio (INR) ≤1.5; Activated Prothrombin Time (APTT) ≤ 1.5 x
- Non-epithelial ovarian cancer, including malignant mixed Mullerian tumors.
- Borderline tumors (tumors of low malignant potential).
- Planned intraperitoneal cytotoxic chemotherapy.
- Prior systemic anticancer therapy for ovarian cancer.
- Any previous radiotherapy to the abdomen or pelvis.
- Patients with synchronous primary endometrial carcinoma, or a past history of primary
endometrial carcinoma, are excluded unless ALL of the following criteria for
describing the endometrial carcinoma are met: Stage ≤ Ib, no more than superficial
myometrial invasion, no lymphovascular invasion, not poorly differentiated (i.e., not
Grade 3 or papillary serous or clear cell).
- Diagnosis of any second malignancy within the last 5 years, except for adequately
treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix
uteri or curatively treated DCIS/LCIS, or non-melanoma or in situ melanoma skin
- Prior treatment with a humanized monoclonal antibody anticancer therapeutic.
- 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.
- Anticipation of a need for a major surgical procedure or radiation therapy during the
- History of hypersensitivity to recombinant proteins.
- Treatment with radiotherapy, surgery, or an investigational agent within 4 weeks of
- Any of the following within 6 months prior to study enrollment: 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, grade ≥ 2 peripheral neuropathy, 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 pregnant (eg, positive human chorionic
gonadotropin test) or is breast feeding.
- Patient of child-bearing potential is not willing to use adequate contraceptive
- Known active infection, or on antiretroviral therapy for HIV disease.
- Known positive test for chronic hepatitis B or C infection.
- Any other underlying physical or mental condition rendering the patient unable to
understand the nature, scope, and possible consequences of the study.
- Refusal or inability to give informed consent to participate in the study.
- 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 study results, and in the judgment of the investigator would make
the patient inappropriate for entry into this study