E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First relapse of platinum-sensitive non-mucinous epithelial ovarian cancer including primary peritoneal or fallopian tube malignancies |
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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 | 10033160 |
E.1.2 | Term | Ovarian epithelial 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 assess the effect of two dose levels of MORAb-003 or placebo in combination with carboplatin and taxane on progression-free survival (PFS), as determined by RECIST, in subjects with platinum-sensitive ovarian cancer in first relapse. |
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E.2.2 | Secondary objectives of the trial |
•To assess the effect of MORAb-003 on overall survival (OS)
•To assess the effect of MORAb-003 on CA-125 defined PFS and serologic response, based on Rustin criteria
•To assess the effect of MORAb-003 to prolong second remission longer than first remission
•To assess the effect of MORAb-003 on best objective response (OR) rate, time to response
(TTR) and duration of response (DR) by RECIST criteria
•To compare the serologic response of low- (1.25 mg/kg) and high- (2.5 mg/kg) dose MORAb-003 to each other in combination with carboplatin and taxane, and to placebo plus carboplatin and taxane
•To assess the safety and tolerability of both dose levels of MORAb-003
•To assess the effect of MORAb-003 on subject-reported on Quality of Life (QoL)
•To assess the effect of MORAb-003 on resource utilization |
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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 |
PHARMACOKINETIC SUB-STUDY IN ASSOCIATION WITH STUDY MORAb-003-004:
•To determine if a pharmacokinetic interaction exists between MORAb-003 and carboplatin, paclitaxel, or docetaxel with a PK drug-drug interaction (DDI) sub-study
PHARMACOGENOMIC SUB-STUDY IN ASSOCIATION WITH STUDY MORAb-003-004:
•Examination of genomic DNA, serum, or archived tumor tissue to identify molecular markers as a surrogate for immunotherapy response. |
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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 histologically or cytologically confirmed diagnosis of non-mucinous epithelial ovarian cancer including primary peritoneal or fallopian tube malignancies
4.Have been treated with debulking surgery and first–line platinum and taxane based chemotherapy
5.Prior bevacizumbab maintenance is allowed. The last dose of bevacizumab must have been at least 30 days before study Day 1. No cytotoxic maintenance therapy (e.g. taxane) or cancer vaccine therapy is allowed.
6.Must have measurable disease by CT or MRI scan
7.Must have relapsed radiologically with a randomization date within ≥6 and ≤ 24 months of completion of first-line platinum/taxane chemotherapy
8.Must be a candidate for repeat carboplatin and taxane therapy
9.Life expectancy of ≥6 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.Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows:
Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L
Platelet count ≥ 100 x 10*9/L
Hemoglobin ≥ 9 g/dL
Creatinine ≤1.5x ULN (CTCAE Grade 1)
Bilirubin < 1.5x ULN (CTCAE Grade 1)
Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase < 2.5 x ULN (CTCAE Grade 1)
13.Neurologic function: neuropathy (sensory and motor) ≤CTCAE Grade 1
14.Subject must provide written informed consent and be able to comply with the protocol procedures
(*=to the power)
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E.4 | Principal exclusion criteria |
1.Subjects who never responded to first-line platinum-based therapy or whose first relapse occurs <6 months or >24 months from the last platinum therapy
2.Subjects who have received other therapy to treat their ovarian cancer since relapse
3.Known central nervous system (CNS) tumor involvement
4.Evidence of other active invasive malignancy requiring treatment in the past 5 years
5.Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months)
6.Electrocardiogram (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 active human immunodeficiency virus (HIV) infection. Asymptomatic positive serology is not exclusionary.
9.Other concurrent immunotherapy (e.g., immunosuppressants or chronic use of systemic corticosteroids with the exception that low-dose corticosteroids are allowed)
10.Known allergic reaction to a prior monoclonal antibody therapy or have any documented HAHA
11.Previous treatment with MORAb-003 (farletuzumab)
12.Clinical contraindications to use of a taxane
13.Prior treatment with any investigational agent within 4 weeks of study entry
14.Breast-feeding, pregnant, or likely to become pregnant during the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) is the primary efficacy endpoint, defined as the time from randomization to progression by RECIST (as measured using independent review of CT/MRI scans as outlined in the Central Radiology Charter and Statistical Analysis Plan), or death from all causes. |
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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. |
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E.5.2 | Secondary end point(s) |
Overall Survival (OS); CA-125 PFS (Rustin Criteria); GCIG PFS
(GCIG Criteria); Tumor Response (OR, TTR, DR per RECIST); Serologic Response (CA-125); length of first versus second remission; Subject-reported Quality of Life (QoL); and Resource utilization [hospitalizations (inpatient or outpatient, length of stay), unscheduled office visits, and admission to hospice or nursing home] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS is defined as the time from the date of randomization to the date of death, due to all causes. 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 earliest.
CA-125 PFS is defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the Rustin criteria, or date of death, whatever the cause.
GCIG PFS is defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the GCIG criteria, or date of death, whatever the cause. |
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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 | Yes |
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 | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 143 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
China |
France |
Germany |
Greece |
Hong Kong |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Philippines |
Poland |
Portugal |
Russian Federation |
Singapore |
Spain |
Switzerland |
Taiwan |
Ukraine |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |