E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The purpose of the study is to compare the 18-month overall survival rate in subjects with advanced melanoma receiving ipilimumab monotherapy (3 mg/kg) as retreatment versus chemotherapy of investigator’s choice in subjects who are randomized at the time of ipilimumab retreatment eligibility. This comparison will be done after the last randomized subject had the chance to be followed for 18 months. |
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E.2.2 | Secondary objectives of the trial |
• To compare overall survival between retreatment with ipilimumab versus chemotherapy of investigator’s choice.
• To compare best overall response rate (BORR by mWHO criteria) between retreatment with ipilimumab versus chemotherapy of investigator’s choice.
• To compare Progression free survival (PFS by mWHO criteria) between retreatment with ipilimumab versus chemotherapy of investigator’s choice.
• To assess the EORTC-QLQ-C30 between retreatment with ipilimumab versus chemotherapy of investigator’s choice. |
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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 |
(1) Pharmacogenetics Blood Sample Amendment Number 01 - Site
Specific (version 1.0, dated 27-Aug-2012)
The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA184243 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of melanoma. Samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective. |
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E.3 | Principal inclusion criteria |
• Histological diagnosis of unresectable stage III or IV metastatic melanoma
• Prior ipilimumab induction treatment (3mg/kg)
• Documented disease control (SD ≥ 3 months or PR/CR) after ipilimumab Induction
• Documented progressive disease following disease control
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E.4 | Principal exclusion criteria |
• Subjects with brain metastasis are excluded, unless they are free of neurologic symptoms related to metastatic brain lesions and do not receive systemic corticosteroid therapy for the purpose of reducing intracranial inflammation in the 10 days prior to beginning retreatment with ipilimumab.
• Any intervening anticancer therapy between last dose of ipilimumab induction and ipilimumab retreatment on study
• Subjects who experienced any grade 3 irAE (except for endocrinopathies where clinical symptoms were controlled with appropriate hormone replacement therapy) or any grade 4 toxicity during prior treatment with ipilimumab.
• Subjects with a prior irAE that has not improved to grade 1 or better atrandomization.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Vital status will be assessed at each study visit. Analysis of Overall Survival will be done once 76 deaths were reported |
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E.5.2 | Secondary end point(s) |
1) Disease Control Rate (DCR)
2) Best Overall Response Rate
3) Assessment of EORTC QLQ-C30 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) and 2) Every three months for approximately 3.5 years after first subject is randomized, then every 6 months
3) At baseline (week 1 prior to first dose), during treatment (every 6 weeks, always prior to dosing), at end of treatment and at all visits thereafter |
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
- Biomarker Assessments (Absolute Lymphocyte Count; Flow Cytometry and Cellular Immune Assays; Serum Cytokines; Tumor Biomarkers);
- Outcomes Research Assessments (QoL instruments: EORTC QLQ-C30; EORTC EQ-5D);
- Health Related Resource Utilization (HRRU) Assessment. |
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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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
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 | 30 |
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 |
Belgium |
France |
Germany |
Italy |
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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The study will remain open until the last subject randomized has been followed for 5 years or the study is terminated by the sponsor. Subjects who discontinue study drug therapy early - due to disease progression or study drug intolerance or for any other reason - will continue to be followed up for survival for 5 years after randomization. |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 1 |