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
- 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
- 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.
- 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
- 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
- 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
- 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.