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
Overview
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 170
- Locations
- 55
- Primary Endpoint
- Progression Free Survival (PFS): Time From Randomization Until Date of Progression or Death.
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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 ≤
- •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.
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, RO
- •Previous exposure to AMG
Arms & Interventions
A
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.
Intervention: AMG 479 Placebo (Drug)
B
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.
Intervention: AMG 479 (Drug)
Outcomes
Primary Outcomes
Progression Free Survival (PFS): Time From Randomization Until Date of Progression or Death.
Time Frame: 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 Outcomes
- Overall Survival (OS)(Day 1 of each cycle up to 4 years after randomization)
- 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)