E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platinum-Resistant or Refractory Relapsed Ovarian Cancer Cáncer de ovario refractario o resistente en recaída a platino |
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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 | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effect of weekly paclitaxel plus MORAb-003 to weekly paclitaxel plus placebo on progression-free survival (PFS) in subjects with relapsed platinum-resistant or refractory ovarian cancer |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of the 2 treatment arms on the following: ?Overall response rate (ORR) ?Overall survival (OS) ?To assess the safety and tolerability of MORAb-003 in combination with weekly paclitaxel ?Changes in CA-125 levels per Gynecologic Cancer Inter Group (GCIG) criteria ?To determine, via a cardiac sub-study, the effect of MORAb-003 cardiac repolarization as defined by the QTcF interval |
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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 |
Cardiac Safety Substudy, 11 March 2009 Amendment 1 |
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E.3 | Principal inclusion criteria |
1. Female subjects ?18 years of age. 2. Subjects of childbearing potential must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period. Contraceptive measures must start either prior to or at screening and continue throughout the entire study period and for 2 months after the last dose of study drug is administered. Pregnant and/or lactating females are excluded. 3. A diagnosis of non-mucinous epithelial ovarian cancer (EOC), including primary peritoneal and fallopian tube malignancies. Must have measurable disease by CT or MRI scan, or progression defined by CA-125 per the modified GCIG criteria (Section 3.1, Table 1), assessed within 4 weeks prior to study entry. 4. Must have been treated with surgery for ovarian cancer and received at least one line of platinum-based chemotherapy. 5. At least one of the lines of platinum containing chemotherapy must have included a taxane. 6. Must have relapsed during or within 6 months of platinum-containing chemotherapy. 7. Subjects may have received up to four additional lines of chemotherapy after they developed platinum-resistance. 8. Subjects must be a candidate for repeat weekly paclitaxel. 9. Life expectancy of ?3 months as estimated by the investigator. 10. Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1. 11. Karnofsky Performance Status (KPS) > 70%. 12. Subjects must not be receiving total parenteral nutrition (TPN) 13. Laboratory test results within the 30 days prior to Study Day 1 as follows: ANC count > 1.5x109/L Platelet count > 100x9/L Hemoglobin > 8g/dL Creatinine <1.5xULN (CTCAE grade 1) Bilirubin < 1.5XULN (CTCAE grade 1) Asparatate aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase <2.5xULN (CTCAE grade 1) 14. Subject must be willing to comply with the protocol and be able to provide written informed consent. |
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E.4 | Principal exclusion criteria |
1. Known central nervous system (CNS) tumor involvement. 2. Clinical contraindications to use of paclitaxel. 3. Evidence of active invasive malignancy other than ovarian cancer requiring treatment in the past 5 years. 4. Current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas). Note: EOC with prior diagnosis of a low malignant potential tumor that has been surgically resected is acceptable provided the subject did not receive prior chemotherapy for any ovarian tumor. 5. Clinically significant heart disease (e.g., congestive heart failure or New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months). 6. ECG demonstrating clinically significant arrhythmias. Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible. 7. Active serious systemic disease, including active bacterial or fungal infection. 8. Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection. Asymptomatic positive serology is not exclusionary. 9. Breast-feeding, pregnant, or likely to become pregnant during the study. 10. Prior radiation therapy is excluded with the exception that it is allowable only if measurable disease for ovarian cancer is completely outside the radiation portal. 11. Other concurrent immunotherapy (e.g., immunosuppressants or chronic use of systemic corticosteroids with the exception of low-dose corticosteroids). 12. Known allergic reaction to a prior monoclonal antibody therapy or have any documented human anti-human antibody (HAHA). 13. Previous treatment with MORAb-003 (farletuzumab). 14. Prior treatment with any investigational agent within 4 weeks of study entry. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Primary: ? PFS based on GCIG criteria, according to both Response Evaluation Criteria in Solid Tumors (RECIST) or CA 125 values
Secondary: ? Overall response rate (based on RECIST or CA-125) ? Overall survival ? Serologic Response (based on Rustin criteria)
Safety: ? Adverse events (including drug hypersensitivity reactions) ? Clinical laboratory tests (serum chemistry, hematology, urinalysis) ? Tolerability (discontinuations, treatment delays, dose reductions) ? Physical examinations (including vital signs assessment) ? Cardiac safety sub-study with a particular emphasis on QTcF interval ? Standard ECG assessments Standard adverse event (AE) monitoring and grading will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0, and coded using Medical Dictionary for Regulatory Activities (MedDRA). |
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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 | No |
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 | No |
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 | Yes |
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) | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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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After 5 month treatment, there will be a follow-up period. Follow-up will be monthly for the first 9 months and then every 2 months until initiation of new therapy for ovarian cancer, death or study termination by the Sponsor |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |