Study of Adding AMG 479 to First Line Chemotherapy in Patients With Optimally Debulked Epithelial Ovarian Cancer

Translational Research In Oncology (TRIO)

Status and phase: Terminated; Phase 2

Conditions: Ovarian Neoplasms

Treatments: Drug: AMG 479; Drug: AMG 479 Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00718523

TRIO 014

Details and patient eligibility

About

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.

Enrollment: 170 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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170 participants in 2 patient groups, including a placebo group

A

Placebo Comparator group

Description:

Placebo plus paclitaxel/carboplatin chemotherapy administered on Day 1 of each 21-day cycle for 6 cycles - then 6 additional cycles of placebo administered on Day 1 of each 21-day cycle.

Treatment:

Drug: AMG 479 Placebo

B

Experimental group

Description:

AMG 479 plus paclitaxel/carboplatin chemotherapy administered on Day 1 of each 21-day cycle for 6 cycles - then 6 additional cycles of AMG 479 single agent administered on Day 1 of each 21-day cycle.

Treatment:

Drug: AMG 479