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

Phase 2

Terminated

Conditions: Ovarian Neoplasms

Interventions: Drug: AMG 479 Placebo
Drug: AMG 479

Registration Number: NCT00718523

Lead Sponsor: Translational Research in Oncology

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 170

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	AMG 479 Placebo	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.
B	AMG 479	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS): Time From Randomization Until Date of Progression or Death.	Radiological tumor assessment: every 12(+/- 1) weeks for 3 years after randomization + CA 125: day 1 of each cycle	A patient may have been declared to have progressive disease on the basis of radiological measuremt of tumor lesions assessmt or CA125 evaluation (tumor measuremts taking precedence).Radiological progression was defined as per the RECIST guidelines (Therasse et al, JNCI2000) as at least 20% increase in the sum of the longest diameters of target lesions(ref the smallest sum of the longest diam recorded since the treatmt started or since the appearance of at least 1 new lesion).Serum CA125 progression was defined, according to the 2005 GCIG def: pts with: * Elevated CA125 pretreatmt and normalization of CA125 has to show evidence of CA125≥ 2 times the upper normal limit on 2 occasions at least 1 wk apart OR * Elevated CA125 pretreatmt which never normalized must show evidence of CA125≥ 2 times the nadir value on 2 occasions at least 1 wk apart OR * CA125 in the normal range pretreatmt had to show evidence of CA125 ≥ 2 times the upper normal limit on 2 occasions at least 1 wk apart

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Day 1 of each cycle up to 4 years after randomization	Interval between the date from randomization to death from any cause whichever came first.
Time To Progression (TTP): Interval From the Date of Randomization to the Date of Disease Progression	Radiological tumor assessment: every 12 (+/- 1) weeks for 3 years after randomization + CA125: day 1 of each cycle	A patient may have been declared to have progressive disease on the basis of radiological measuremt of tumor lesions assessmt or CA125 evaluation (tumor measuremts taking precedence).Radiological progression was defined as per the RECIST guidelines (Therasse et al, JNCI2000) as at least 20% increase in the sum of the longest diameters of target lesions(ref the smallest sum of the longest diam recorded since the treatmt started or since the appearance of at least 1 new lesion).Serum CA125 progression was defined, according to the 2005 GCIG def: pts with: * Elevated CA125 pretreatmt and normalization of CA125 has to show evidence of CA125≥ 2 times the upper normal limit on 2 occasions at least 1 wk apart OR * Elevated CA125 pretreatmt which never normalized must show evidence of CA125≥ 2 times the nadir value on 2 occasions at least 1 wk apart OR * CA125 in the normal range pretreatmt had to show evidence of CA125 ≥ 2 times the upper normal limit on 2 occasions at least 1 wk apart

Trial Locations

Locations (55): Central Hematology Oncology Medical Group Inc.
🇺🇸
Alhambra, California, United States
Providence Saint Joseph Medical Center
🇺🇸
Burbank, California, United States
St Jude Heritage Healthcare
🇺🇸
Fullerton, California, United States
Wilshire Oncology Medical Group Inc
🇺🇸
La Verne, California, United States
University of Southern California
🇺🇸
Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
UCLA
🇺🇸
Los Angeles, California, United States
North Valley Hematology/Oncology Medical Group
🇺🇸
Northridge, California, United States
Ventura County Hematology-Oncology Specialists
🇺🇸
Oxnard, California, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
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Central Hematology Oncology Medical Group Inc.
🇺🇸Alhambra, California, United States