E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic renal cell carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Advanced or metastatic renal cell carcinoma |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038414 |
E.1.2 | Term | Renal cell carcinoma stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10038408 |
E.1.2 | Term | Renal cell carcinomas |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is to compare the progression free survival and the overall survival of nivolumab combined with ipilimumab to sunitinib monotherapy in patients with previously untreated Renal Cell Cancer. |
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E.2.2 | Secondary objectives of the trial |
1.Progression-free survival
2.Overall survival
3.Objective response rate
4.Duration of objective response
5.Overall safety & tolerability
6.Disease related symptom progression
7.Health related quality of life
8.Healthcare 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 |
Pharmacogenetics Blood Sample Amendment 01 dated 17-jul-2014, version 1.0
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, CA209214 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 renal cell carcinoma. 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 |
Key Inclusion Criteria:
-Histological confirmation of RCC with a clear-cell component
-Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
-No prior systemic therapy for RCC with the following exception:
a) One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets VEGF or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy.
-Karnofsky Performance Status (KPS) of at least 70%
-Measurable disease as per RECIST 1.1
-Tumor tissue (formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition) must be received by the central vendor (block or unstained slides) in order to randomize a subject to study treatment. (Note: Fine Needle Aspiration [FNA] and bone metastases samples are not acceptable for submission).
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria:
-Any history of or current CNS metastases. Baseline imaging of the brain is required within 28 days prior to randomization.
-Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, sunitinib, pazopanib, axitinib, tivozanib, and bevacizumab).
-Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
-Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
-Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are overall survival and progression free survival. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Progression will be assessed beginning 12 wks after randomization and continuing every 6 weeks during the first 13 months and every 12 wks thereafter.
-Overall survival will be followed every 2 weeks while on treatment and then every 3 months. |
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E.5.2 | Secondary end point(s) |
1) Progression-free survival
2) Overall survival
3) Objective response rate
4) Duration of objective response
5) Overall safety & tolerability
6) Disease related symptom progression
7) Health related quality of life
8) Healthcare resource utilization |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) see E.5.1.1
2) see E.5.1.1
3) 12 wks after randomization and continuing every 6 weeks during the first 13 months and every 12 wks thereafter
4) same as 3)
5) Continuously throughout treatment and for 100 days post treatment
6) Baseline, and then twice per 6 week cycle for first 6 months and then every 6 weeks after for duration of treatment and then every 3 months for the first 12 months of the follow-up period and then 6 monthly after that.
7) Baseline, and then twice per 6 week cycle for first 6 months and then every 6 weeks after for duration of treatment
8) same as 7) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 81 |
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 |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Mexico |
Netherlands |
Poland |
Spain |
Sweden |
Turkey |
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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Last follow-up visit of the last patient |
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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 | 10 |
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 |