Study of Adding AMG 479 to First Line Chemotherapy in Patients With Optimally Debulked Epithelial Ovarian Cancer
Condition: Ovarian Neoplasms
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: AMG 479; AMG 479 Placebo
Intervention description: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle; Matching placebo administered Day 1 of each 21 day cycle.
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 170.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will determine the value of adding AMG 479 (fully human monoclonal antibody
      against IGF-1R) to paclitaxel and carboplatin first line chemotherapy in patients with
      optimally debulked (<1 cm) FIGO stage III and IV (positive pleural cytology only) ovarian
      epithelial (including fallopian tube and primary peritoneal) carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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
             mg/dL.

          -  Patient must be willing and able to comply with scheduled visits, and all study
             procedures.

          -  Informed consent obtained.

          -  Patients should be able to commence systemic therapy within 6 weeks of cytoreductive
             surgery.

          -  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 ULN

        Exclusion Criteria:

          -  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
             cancer.

          -  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
             study.

          -  History of hypersensitivity to recombinant proteins.

          -  Treatment with radiotherapy, surgery, or an investigational agent within 4 weeks of
             randomization.

          -  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
             precautions.

          -  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