| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early stage localized Renal Cell Carcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Early stage localized renal cancer |
|
| 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 | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10038395 |
| E.1.2 | Term | Renal carcinoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
Part A: TTo compare disease-free survival (DFS) per Blinded
Independent Central Review (BICR) of nivolumab combined with
ipilimumab versus placebo infusions in participants with localized RCC, with a predominantly clear cell histology, who have undergone a nephrectomy
Part B: To compare disease-free survival (DFS) per Blinded Independent Central Review (BICR) of nivolumab versus placebo infusions in participants with localized renal cell carcinoma, with a predominantly clear cell histology who have undergone nephrectomy. |
|
| E.2.2 | Secondary objectives of the trial |
1) • Part A: To compare OS, including the 5-year OS
rates, of nivolumab combined with ipilimumab versus placebo infusions in participants with localized renal cell carcinoma with a predominantly clear cell histology who have undergone a nephrectomy
• Part B: To compare OS, including the 5-year OS
rates, of nivolumab versus placebo infusions in participants with
localized renal cell carcinoma with a predominantly clear cell histology who have undergone a nephrectomy
• Part B: To evaluate differences in disease-free survival (DFS) per
Blinded Independent Central Review (BICR) and overall survival (OS) of contemporaneously randomized nivolumab combined with ipilimumab participants versus nivolumab participants with localized renal cell carcinoma, with a predominantly clear cell histology, who have undergone a nephrectomy.
2) To describe the safety and tolerability of nivolumab combined with ipilimumab and nivolumab monotherapy up to 30 and 100 days of last dose of study therapy. |
|
| 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 |
Additional research is optional for all study participants, except where retention and/or collection is prohibited by local laws or regulations, ethics committees, or institutional requirements.
This collection for additional research is intended to expand the translational R&D capability at Bristol-Myers Squibb, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression and response to treatment etc. |
|
| E.3 | Principal inclusion criteria |
a) Kidney tumor has been completely resected with negative surgical
margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy. Partial nephrectomy is allowed provided all inclusion criteria are met.
b) Post-nephrectomy tumor shows RCC with a predominately clear cell histology, including participants with sarcomatoid features.
c) Pathological TNM staging per AJCC staging version 2010: (refer to Appendix 9 for correlations of classifications in cancer staging systems):
♦ pT2a, G3 or G4, N0M0
♦ pT2b, G any, N0M0
♦ pT3, (a, b, c), G any, N0M0
♦ pT4, G any, N0M0
♦ pT any, G any, N1M0
d) Participants must have no clinical or radiological evidence of
macroscopic residual disease or distant metastases (M0) after nephrectomy
i) Baseline tumor assessment, performed 4 to approximately 12 weeks
after nephrectomy, shows no metastasis or residual tumor lesions per
local review and as confirmed by Blinded Independent Central Review (BICR). Results of BICR of the baseline tumor assessment confirming absence of metastasis or residual tumor lesions must be received before randomization.
ii) If the Investigator is not certain the participant is disease free, the participant should:
1) not be consented or be enrolled into the study and 2) evaluation for eligibility should not be submitted to BICR.
Note: participants with one or more regional lymph nodes identified with short axis 15 mm on the baseline (post-operative) tumor assessments are considered to have gross residual disease and are therefore ineligible.
e) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
f) Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or
unstained tumor tissue sections, obtained within 3 months prior to
enrollment, preferably from nephrectomy, with an associated pathology report, must be submitted to the central laboratory prior to randomization. FFPE block or 20 unstained slides is ideal, but a minimum of 10 unstained slides will be acceptable if tumor tissue is limited. Biopsy should be excisional, incisional, or core needle. Fine needle aspiration is unacceptable for submission |
|
| E.4 | Principal exclusion criteria |
a) Any severe or serious, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration including ongoing or active infection requiring parental antibiotics
b) Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Topical, ocular, intra-articular, intranasal, inhaled steroids, and adrenal replacement steroid doses > 10 mg daily prednisone or the
equivalent are permitted in the absence of active immune disease.
c) Uncontrolled adrenal insufficiency
d) Participants with an active known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is DFS (disease-free survival). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoint of DFS will be programmatically determined based on the disease recurrence date provided by the BICR. DFS is defined as the time from randomization to development of local disease recurrence (ie, recurrence of primary tumor in situ or occurrence of a secondary RCC primary cancer), distance metastasis, or death, whichever came first. |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• OS, defined as the time between the date of randomization and the
date of death. For participants without documentation of death, OS will
be censored on the last date the participants was known to be alive.
• DFS and OS in contemporaneously randomized combination and
monotherapy participants. |
|
| 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 | No |
| 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 | 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 | No |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| 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 |
| Brazil |
| Canada |
| Mexico |
| Peru |
| Singapore |
| Switzerland |
| Russian Federation |
| Austria |
| Belgium |
| Czechia |
| France |
| Germany |
| Hungary |
| Italy |
| Netherlands |
| Poland |
| Spain |
| United Kingdom |
|
| 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
|
| End of trial is defined as the last participant’s last study visit or phone call. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 14 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 25 |
| E.8.9.2 | In all countries concerned by the trial years | 15 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 24 |
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