E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic Melanoma |
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E.1.1.1 | Medical condition in easily understood language |
Unresectable or metastatic Melanoma |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary purpose of this study is to compare the objective response rate (ORR), as determined by investigators, of nivolumab combined with ipilimumab versus ipilimumab monotherapy in subjects with unresectable or metastatic melanoma. |
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E.2.2 | Secondary objectives of the trial |
- Investigator-assessed progression-free survival in BRAF WT subjects
- Investigator-assessed objective response rate and progression-free survival in BRAF mutant subjects
- Changes from baseline in the EORTC QLQ-C30 global health status/QoL composite scale. |
|
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 |
Pharmacogenetics Blood Sample Protocol Amendment 01, version 1.0, dated 07-May-2013
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, CA209069 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 |
-ECOG PS 0 or 1.
- Histologically confirmed unresectable Stage III or Stage IV Melanoma, as per AJCC staging system
- No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized.
- Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses. In order to be treated, tumor tissue should be received by the central laboratory. In the event that lab kits are not available on-site when a subject meets all other criteria to begin treatment, the subject may begin treatment prior to tissue having been received by the central lab. In such cases, tissue should be sent to the central lab as soon as kits become available.
-Known BRAF V600 mutation status. Subjects with either V600 wild-type or V600 mutation-melanoma are eligible. |
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E.4 | Principal exclusion criteria |
- Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
-Ocular melanoma
- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is objective response rate (ORR) as determined by investigators in BRAF WT subjects |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, Week 12, every 6 weeks thereafter up to week 49, and then every 12 weeks until disease progression is documented (expected to be no more than 5 years) |
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E.5.2 | Secondary end point(s) |
- Investigator-assessed progression-free survival in BRAF WT subjects
- Investigator-assessed objective response rate and progression-free survival in BRAF mutant subjects
- Changes from baseline in the EORTC QLQ-C30 global health status/QoL composite scale. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Baseline, Week 12, every 6 weeks thereafter up to week 49, and then every 12 weeks until disease progression is documented (expected to be no more than 5 years)
-Baseline, Week 12, every 6 weeks thereafter up to week 49, and then every 12 weeks until disease progression is documented (expected to be no more than 5 years)
-Baseline, every 6 weeks for the first 6 months. |
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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, Outcomes Research assessments, Immunogenicity assessments. |
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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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Nivolumab combined with Ipilimumab versus Ipilimumab alone |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
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 |
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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
|
The study will end once survival follow-up has concluded |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
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 | 7 |