ivolumab combined with ipilimumab versus sunitinib in previously untreated advanced or metastatic renal cell carcinoma.

Phase 1

Conditions: Advanced or metastatic renal cell carcinoma
MedDRA version: 21.1Level: PTClassification code 10038414Term: Renal cell carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 11.0Level: HLTClassification code 10038408Term: Renal cell carcinomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001750-42-FI

Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1355

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).
Please refer to section 3.1.1 regarding inclusion criteria for the Crossover Extension Phase (arm B only)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 840
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 515

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.
Please refer to section 3.1.1 regarding exclusion criteria for the Crossover Extension Phase (arm B only)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: 1.Progression-free survival<br>2.Overall survival <br>3.Objective response rate<br>4.Duration of objective response<br>5.Overall safety & tolerability<br>6.Disease related symptom progression<br>7.Health related quality of life<br>8.Healthcare resource utilization;Primary end point(s): The primary endpoints are overall survival and progression free survival.;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. <br>-Overall survival will be followed every 2 weeks while on treatment and then every 3 months.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Progression-free survival<br>2) Overall survival <br>3) Objective response rate<br>4) Duration of objective response<br>5) Overall safety & tolerability<br>6) Disease related symptom progression<br>7) Health related quality of life<br>8) Healthcare resource utilization<br>9) Adverse Event Incidence Rate;Timepoint(s) of evaluation of this end point: 1) see E.5.1.1<br>2) see E.5.1.1<br>3) 12 wks after randomization and continuing every 6 weeks during the first 13 months and every 12 wks thereafter <br>4) same as 3)<br>5) Continuously throughout treatment and for 100 days post treatment<br>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. <br>7) Baseline, and then twice per 6 week cycle for first 6 months and then every 6 weeks after for duration of treatment<br>8) same as 7)<br>9) Up to 61 months

Related Trials