Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

A Phase 3, Randomized, Open-Label Study of Nivolumab Combined With Ipilimumab Versus Sunitinib Monotherapy in Subjects With Previously Untreated, Advanced or Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02231749
• Other study ID #: CA209-214
• Secondary ID: 2014-001750-42
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 16, 2014
• Est. completion date: August 7, 2027

Study information

• Verified date: November 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the objective response rate, progression free survival and the overall survival of Nivolumab combined with Ipilimumab to Sunitinib monotherapy in patients with previously untreated Renal Cell Cancer.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1390
• Est. completion date: August 7, 2027
• Est. primary completion date: June 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histological confirmation of renal cell carcinoma (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:

1. One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets vascular endothelial growth factor (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 Response Evaluation Criteria in Solid Tumors (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)

Exclusion Criteria:

• Any history of or current central nervous system (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-programmed death (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte antigen 4 (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

Related Conditions & MeSH terms

• Advanced Renal Cell Carcinoma
• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Intervention

Biological:
• Nivolumab

• Ipilimumab

Drug:
• Sunitinib

Locations

Country	Name	City	State
Argentina	Local Institution - 0099	Berazategui	Buenos Aires
Argentina	Local Institution - 0097	Caba
Argentina	Local Institution - 0098	Capital Federal	Buenos Aires
Argentina	Local Institution - 0139	Ciudad Autonoma De Buenos Aire	Buenos Aires
Argentina	Local Institution - 0100	Cordoba
Argentina	Local Institution - 0095	San Miguel De Tucuman	Tucuman
Argentina	Local Institution - 0096	San Miguel de Tucuman	Tucuman
Australia	Local Institution - 0072	Box Hill	Victoria
Australia	Local Institution - 0071	Clayton	Victoria
Australia	Local Institution - 0140	Elizabeth Vale	South Australia
Australia	Local Institution - 0076	Herston	Queensland
Australia	Local Institution - 0073	Kogarah	New South Wales
Australia	Local Institution - 0074	Murdoch
Australia	Local Institution - 0104	Nedlands	Western Australia
Australia	Local Institution - 0075	Southport	Queensland
Australia	Local Institution - 0070	Westmead	New South Wales
Austria	Local Institution - 0108	Linz
Austria	Local Institution - 0107	Wels
Austria	Local Institution - 0109	Wien
Belgium	Local Institution - 0020	Gent
Belgium	Local Institution - 0019	Leuven
Brazil	Local Institution - 0152	Belo Horizonte	Minas Gerais
Brazil	Local Institution - 0150	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0151	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution - 0157	Rio de Janeiro
Brazil	Local Institution - 0153	Sao Paulo	São Paulo
Brazil	Local Institution - 0155	Sao Paulo
Brazil	Local Institution - 0156	Sao Paulo
Canada	Local Institution - 0149	Calgary	Alberta
Canada	Local Institution - 0133	Edmonton	Alberta
Canada	Local Institution - 0182	Kelowna	British Columbia
Canada	Local Institution - 0131	Moncton	New Brunswick
Canada	Local Institution - 0132	Montreal	Quebec
Canada	Local Institution - 0148	Toronto	Ontario
Canada	Local Institution - 0172	Toronto	Ontario
Canada	Local Institution - 0128	Vancouver	British Columbia
Chile	Local Institution - 0101	Santiago	Metropolitana
Chile	Local Institution - 0102	Santiago	Metropolitana
Chile	Local Institution - 0144	Santiago	Metropolitana
Chile	Local Institution - 0103	Vina del Mar
Colombia	Local Institution - 0080	Bogota
Colombia	Local Institution - 0081	Medellin
Colombia	Local Institution - 0162	Medellin
Czechia	Local Institution - 0053	Brno
Czechia	Local Institution - 0051	Hradec Kralove
Czechia	Local Institution - 0050	Liberec	Liberecký Kraj
Czechia	Local Institution - 0052	Olomouc
Denmark	Local Institution - 0136	Aarhus N
Denmark	Local Institution - 0158	Herlev
Denmark	Local Institution - 0137	Odense
Finland	Local Institution - 0027	Helsinki	Uusimaa
Finland	Local Institution - 0028	Tampere
France	Local Institution - 0170	Besançon
France	Local Institution - 0062	Bordeaux
France	Local Institution - 0169	La Roche-Sur-Yon Cedex 9
France	Local Institution - 0060	Marseille Cedex 9
France	Local Institution - 0061	Paris	Île-de-France
France	Local Institution - 0063	Saint Herblain
France	Local Institution - 0065	Strasbourg
France	Local Institution - 0059	Toulouse Cedex 9
France	Local Institution - 0058	Villejuif
Germany	Local Institution - 0125	Aachen
Germany	Local Institution - 0126	Erlangen
Germany	Local Institution - 0141	Frankfurt
Germany	Local Institution - 0147	Hamburg
Germany	Local Institution - 0142	Hannover
Germany	Local Institution - 0123	Heidelberg
Germany	Local Institution - 0127	Homburg
Germany	Local Institution - 0129	Jena
Germany	Local Institution - 0143	Magdeburg
Germany	Local Institution - 0124	Muenchen
Germany	Local Institution - 0146	Muenster
Germany	Local Institution - 0130	Ulm
Hungary	Local Institution - 0083	Budapest
Hungary	Local Institution - 0082	Debrecen
Hungary	Local Institution - 0184	Gyula	Békés
Hungary	Local Institution - 0084	Pecs
Ireland	Local Institution - 0016	Dublin
Ireland	Local Institution - 0017	Dublin 7	Dublin
Ireland	Local Institution - 0018	Dublin 7	Dublin
Ireland	Local Institution - 0015	Wilton	Cork
Israel	Local Institution - 0120	Haifa
Israel	Local Institution - 0117	Kfar Saba
Israel	Local Institution - 0121	Petach Tikva
Israel	Local Institution - 0118	Ramat-gan
Israel	Local Institution - 0119	Zerifin
Italy	Local Institution - 0022	Arezzo
Italy	Local Institution - 0024	Meldola (fc)
Italy	Local Institution - 0023	Milano
Italy	Local Institution - 0064	Napoli
Italy	Local Institution - 0079	Padova
Italy	Local Institution - 0025	Pavia
Italy	Local Institution - 0026	Roma
Japan	Local Institution - 0192	Akita-shi	Akita
Japan	Local Institution - 0195	Bunkyo-ku	Tokyo
Japan	Local Institution - 0197	Bunkyo-ku	Tokyo
Japan	Local Institution - 0202	Bunkyo-ku	Tokyo
Japan	Local Institution - 0187	Chiba-shi	Chiba
Japan	Local Institution - 0196	Fukuoka-shi	Fukuoka
Japan	Local Institution - 0208	Hamamatsu-shi	Shizuoka
Japan	Local Institution - 0209	Hirosaki-shi	Aomori
Japan	Local Institution - 0206	Kobe	Hyogo
Japan	Local Institution - 0207	Koto-ku	Tokyo
Japan	Local Institution - 0189	Kumamoto-shi	Kumamoto
Japan	Local Institution - 0191	Kyoto-shi	Kyoto
Japan	Local Institution - 0200	Morioka-shi	Iwate
Japan	Local Institution - 0199	Niigata-shi	Niigata
Japan	Local Institution - 0204	Okayama-shi	Okayama
Japan	Local Institution - 0190	Osaka-sayama	Osaka
Japan	Local Institution - 0183	Sapporo-shi	Hokkaido
Japan	Local Institution - 0188	Sapporo-shi	Hokai-do
Japan	Local Institution - 0185	Shinjuku-Ku	Tokyo
Japan	Local Institution - 0193	Shinjuku-ku	Tokyo
Japan	Local Institution - 0201	Suita-shi	Osaka
Japan	Local Institution - 0194	Tokushima-shi	Tokushima
Japan	Local Institution - 0198	Tokyo
Japan	Local Institution - 0205	Tsukuba-shi	Ibaraki
Japan	Local Institution - 0203	Yamagata
Japan	Local Institution - 0186	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution - 0176	Seoul
Korea, Republic of	Local Institution - 0177	Seoul
Korea, Republic of	Local Institution - 0178	Seoul
Mexico	Local Institution - 0168	Mexico D.f.	Distrito Federal
Mexico	Local Institution - 0171	Monterrey	Nuevo Leon
Mexico	Local Institution - 0167	Oaxaca
Mexico	Local Institution - 0175	Queretaro	Querétaro
Netherlands	Local Institution - 0029	Amsterdam
Netherlands	Local Institution - 0040	Groningen
Netherlands	Local Institution - 0030	Nijmegen
Poland	Local Institution - 0093	Krakow
Poland	Local Institution - 0112	Poznan
Poland	Local Institution - 0106	Wroclaw
Spain	Local Institution - 0088	Barcelona
Spain	Local Institution - 0089	Barcelona
Spain	Local Institution - 0085	Madrid
Spain	Local Institution - 0086	Madrid
Spain	Local Institution - 0087	Madrid
Spain	Local Institution - 0111	Oviedo
Spain	Local Institution - 0090	Sevilla
Sweden	Local Institution - 0134	Solna
Taiwan	Local Institution - 0179	Taipei
Taiwan	Local Institution - 0180	Taipei
Taiwan	Local Institution - 0181	Taoyuan
Turkey	Local Institution - 0115	Ankara
Turkey	Local Institution - 0114	Antalya
Turkey	Local Institution - 0122	Istanbul
United Kingdom	Local Institution - 0009	Glasgow	Lanarkshire
United Kingdom	Local Institution - 0010	London	Greater London
United Kingdom	Local Institution - 0077	London
United Kingdom	Local Institution - 0021	Manchester
United Kingdom	Local Institution - 0011	Northwood
United Kingdom	Local Institution - 0012	Swansea
United States	Local Institution - 0054	Allentown	Pennsylvania
United States	Local Institution - 0046	Ann Arbor	Michigan
United States	Local Institution - 0068	Atlanta	Georgia
United States	Local Institution - 0004	Baltimore	Maryland
United States	Local Institution - 0048	Baltimore	Maryland
United States	Local Institution - 0110	Boston	Massachusetts
United States	Local Institution - 0135	Boston	Massachusetts
United States	Local Institution - 0161	Boston	Massachusetts
United States	Local Institution - 0173	Boston	Massachusetts
United States	Local Institution - 0036	Buffalo	New York
United States	Local Institution - 0055	Charleston	South Carolina
United States	Local Institution - 0008	Charlotte	North Carolina
United States	Local Institution - 0159	Chattanooga	Tennessee
United States	Local Institution - 0007	Cleveland	Ohio
United States	Local Institution - 0164	Columbus	Ohio
United States	Local Institution - 0032	Dallas	Texas
United States	Local Institution - 0056	Dallas	Texas
United States	Local Institution - 0043	Detroit	Michigan
United States	Local Institution - 0006	Duarte	California
United States	Local Institution - 0045	Durham	North Carolina
United States	Local Institution - 0163	Fairway	Kansas
United States	Local Institution - 0003	Houston	Texas
United States	Local Institution - 0038	Indianapolis	Indiana
United States	Local Institution - 0042	Iowa City	Iowa
United States	Local Institution - 0057	La Jolla	California
United States	Local Institution - 0035	Los Angeles	California
United States	Local Institution - 0044	Los Angeles	California
United States	Local Institution - 0066	Nashville	Tennessee
United States	Local Institution - 0138	New Haven	Connecticut
United States	Local Institution - 0001	New York	New York
United States	Local Institution - 0005	Philadelphia	Pennsylvania
United States	Local Institution - 0031	Pittsburgh	Pennsylvania
United States	Local Institution - 0039	Portland	Oregon
United States	Local Institution - 0041	Seattle	Washington
United States	Local Institution - 0067	Stanford	California
United States	Local Institution - 0049	Tampa	Florida
United States	Local Institution - 0034	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator-assessed Objective Response Rate(ORR) in Intermediate/Poor Risk Participants Per IRRC Using RECIST v1.1	ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on IRRC assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months)
Primary	Overall Survival (OS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	OS was defined as the time from randomization to the date of death from any cause. Survival time was censored at the date of last contact ("last known alive date") for subjects who were alive.	From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months)
Primary	Progression-Free Survival (PFS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.	From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months)
Secondary	Investigator-assessed Objective Response Rate(ORR) in Any Risk Participants Per IRRC Using RECIST v1.1	ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on IRRC assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months)
Secondary	Overall Survival (OS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	Overall survival is defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time will be censored at the date of last contact ("last known alive date"). Overall survival will be censored for subjects at the date of randomization if they were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after subject's off-treatment date.	From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months)
Secondary	Progression-Free Survival (PFS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.	From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls