E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platinum-Resistant or Refractory Relapsed Ovarian Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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) as determined by RECIST and overall survival (OS) 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:
•PFS based on GCIG criteria (original primary efficacy endpoint)
•Overall response rate (ORR) based on RECIST criteria (key secondary objective)
•Serologic response based on modified Rustin criteria
•To assess the safety and tolerability of MORAb-003 in combination with weekly paclitaxel
Exploratory Objective:
•Examination of genomic DNA, serum, or archived tumor tissue to identify molecular markers as a surrogate for immunotherapy response.
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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 |
Molecular Marker substudy- included in the protocol of the study Version Amendment 3, 23 February 2010 |
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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 test article 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 per RECIST criteria, assessed within 4 weeks prior to study entry.
4. Must have been treated with debulking 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 evidence of relapse by CA-125 (2xULN) or radiographically during or within 6 months of most recent 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 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 > 100x109/L
Hemoglobin > 8g/dL
Creatinine <1.5x upper limit of normal (ULN) (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:
Co-Primary:
• PFS based on RECIST criteria
• OS
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS is defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the independent radiologic assessment (RECIST), or date of death, whatever the cause. If progression or death is not observed for a subject, the PFS time will be censored at the date of last tumor assessment without evidence of progression prior to the date of initiation of further anti-tumor treatment, or the cut-off date, whichever is earliest.
OS is defined as the time (in months) from the date of randomization to the date of death, whatever the cause. If death is not observed for a subject, the survival time will be censored on the last date known to be alive or the cut-off date, whichever is earlier.
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E.5.2 | Secondary end point(s) |
Secondary:
• PFS based on GCIG criteria
• Overall response rate (based on RECIST criteria)
• Serologic response (based on modified Rustin criteria)
• To assess the safety and tolerability of MORAb-003 in combination with weekly paclitaxel
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
GCIG PFS is defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the GCIG criteria, or date of death, whatever the cause. If progression or death is not observed for a subject, the GCIG PFS time will be censored at the later date of last tumor assessment or CA-125 assessment without evidence of progression prior to the date of initiation of further anti-tumor treatment or the “Survival cut-off” date, whichever is earliest.
Objective response (OR) is defined as either a confirmed complete response (CR) or confirmed partial response (PR) using RECIST criteria.
Serologic response (SR) is defined either as normalization, 75% response, or 50% response using modified Rustin criteria. |
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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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | No |
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 |
Australia |
Belgium |
Canada |
Netherlands |
Spain |
United States |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |