A randomized, double-blind, placebo controlled, multicenter, 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 ( < 1cm) epithelial ovarian cancer
- Conditions
- Optimally debulked epithelial ovarian cancerMedDRA version: 9.1Level: LLTClassification code 10033128Term: Ovarian cancer
- Registration Number
- EUCTR2008-001551-22-FR
- Lead Sponsor
- Cancer International Research Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 170
- 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 as evidenced by:
- hemoglobin = 9.0 g/dL,
- absolute neutrophil count = 1.5 x 109/L,
- platelet count = 100 x 109/L,
- Serum creatinine = 1.5 x ULN and measured or calculated creatinine clearance = 60 mL/min.
- AST and ALT = 2.5 x ULN
- total bilirubin = 1.5 x ULN unless increase is due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin,
- 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
- 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.
- 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To estimate whether the addition of AMG 479 to paclitaxel and carboplatin chemotherapy improves progression free survival (PFS) when compared to paclitaxel and carboplatin chemotherapy alone;Secondary Objective: - To assess time to progression (TTP),<br>- To assess overall survival (OS),<br>- To assess the safety profile of AMG 479,<br>- To assess health-related quality of life (HRQL),<br>- To assess the pharmacokinetics (PK) of AMG 479 and paclitaxel/carboplatin,<br>- To assess patients for the development of anti-AMG 479 antibodies;Primary end point(s): Progression Free Survival = time from randomization until date of progression or death . (Date of progression = date of the first imaging or clinical exam or biochemical occurence showing disease progression. Progression definition is based on radiological tumor assessment and CA 125 biomarker progression).<br>
- Secondary Outcome Measures
Name Time Method