E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Optimally debulked epithelial ovarian cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
- To assess time to progression (TTP), - To assess overall survival (OS), - To assess the safety profile of AMG 479, - To assess health-related quality of life (HRQL), - To assess the pharmacokinetics (PK) of AMG 479 and paclitaxel/carboplatin, - To assess patients for the development of anti-AMG 479 antibodies |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Whole Blood Collection - final version dated 6th June 2008 - To develop markers to identify disease subtypes, guide therapy and/or predict disease progression and for pharmacogenomics purpose.
- Intensive pharmacokinetics - final version dated 6th June 2008 - To assess the pharmacokinetics of AMG 479 and paclitaxel/carboplatin. |
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E.3 | Principal 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 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.
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E.4 | Principal 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. - 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
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E.5 End points |
E.5.1 | 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).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 12 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |