A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

Phase 3

Active, not recruiting

• Conditions: Renal Cell Carcinoma
• Interventions: Biological: Nivolumab; Biological: Ipilimumab; Drug: Sunitinib; Drug: Cabozantinib

• Registration Number: NCT03141177
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in previously untreated advanced or metastatic renal cell carcinoma

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-03
• Study First Submitted QC: 2017-05-03
• Study First Posted: 2017-05-04
• Study Start: 2017-08-22
• Primary Completion: 2020-02-12
• Disposition First Submitted: 2021-02-11
• Results First Submitted: 2022-02-11
• Results First Submitted QC: 2022-03-29
• Disposition First Submitted QC: 2022-03-29
• Results First Posted: 2022-04-26
• Disposition First Posted: 2022-04-26
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-12
• Last Update Posted: 2024-01-17
• Study Completion: 2024-04-17

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 701

Inclusion Criteria

• Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid features

• 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:

  i) 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

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Exclusion Criteria

• Any active CNS metastases
• Any active, known or suspected autoimmune disease
• Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
• Participants who have received a live/attenuated vaccine within 30 days of first treatment

Other protocol defined inclusion/exclusion criteria could apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Doublet	Nivolumab	Nivolumab and Cabozantinib
Triplet	Ipilimumab	Nivolumab, Ipilimumab, Cabozantinib \*Enrollment to the triplet arm was discontinued by protocol amendment
Doublet	Cabozantinib	Nivolumab and Cabozantinib
Monotherapy	Sunitinib	Sunitinib

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months)	PFS is defined as the time from date of randomization to the first documented tumor progression date or death due to any cause, whichever occurs first based on BICR assessment using RECIST v1.1. Participants who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment on or prior to initiation of subsequent anti-cancer therapy. Progressive disease (PD); 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study

Secondary Outcome Measures

Name	Time	Method
Number of Deaths	From first dose to (up to 31 months) following first dose	Number of deaths due to any cause during the specified time frame.
Number of Participants Experiencing Serious Adverse Events (SAEs)	From first to dose to 100 days following last dose (Up to 32 months)	Number of participants experiencing various types of any grade serious adverse events (SAEs) during the specified time frame.
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation	From first dose to 30 days following last dose (Up to 30 months)	Number of participants experiencing various types of any grade adverse events (AEs) leading to discontinuation during the specified time frame.
Objective Response Rate (ORR)	Up to 31 Months	Objective Response Rate (ORR) is defined as the percentage of randomized participants who achieve a best response of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1 criteria) divided by the number of all randomized participants.; Complete response (CR): Disappearance of all target lesions. Partial response (PR): 30% decrease in the sum of diameters of target lesions.
Overall Survival (OS)	From randomization date to death date (Up to 31 months)	Overall Survival is defined as the time between the date of randomization and the date of death due to any cause. For participants that are alive, their survival time will be censored at the date of last contact date (or "last known alive date").
Number of Participants Experiencing Adverse Events (AEs)	From first dose to 100 days following last dose (Up to 32 Months)	Number of participants experiencing various types of any grade adverse events (AEs) during the specified time frame.
Number of Participants With Laboratory Abnormalities	From first dose to 30 days following last dose (Up to 30 Months)	Number of participants experiencing laboratory abnormalities in hematology, serum chemistry and electrolytes with grade 3 or higher during the specified time frame.
Number of Participants With Laboratory Values Grade Shifting From Baseline	From first dose to 30 days following last dose (Up to 30 Months)	Number of participants experiencing worsening shift from baseline in any grade and grade 3-4 of laboratory values during the specified time frame.

Trial Locations

Locations (135)

Local Institution - 0125; 🇪🇸 Barcelona, Spain

Local Institution - 0121; 🇪🇸 Madrid, Spain

Local Institution - 0001; 🇦🇺 Southport, Queensland, Australia

Local Institution - 0103; 🇺🇸 Aurora, Colorado, United States

Local Institution - 0088; 🇺🇸 San Luis Obispo, California, United States

Local Institution - 0129; 🇦🇺 South Brisbane, Australia

Central Coast Medical Oncology Corporation; 🇺🇸 Santa Maria, California, United States

Local Institution - 0035; 🇺🇸 Saint Louis, Missouri, United States

Local Institution - 0078; 🇺🇸 Sherman, Texas, United States

Local Institution - 0017; 🇺🇸 New York, New York, United States

Local Institution - 0090; 🇺🇸 Redondo Beach, California, United States

Local Institution - 0074; 🇧🇷 Sao Paulo, Brazil

Local Institution - 0067; 🇺🇸 Portland, Oregon, United States

Local Institution - 0005; 🇦🇺 Malvern, Victoria, Australia

Local Institution - 0086; 🇺🇸 Newnan, Georgia, United States

Local Institution - 0106; 🇺🇸 Kansas City, Missouri, United States

Local Institution - 0127; 🇺🇸 Athens, Georgia, United States

Local Institution - 0058; 🇧🇷 Barretos, Sao Paulo, Brazil

Local Institution - 0046; 🇦🇷 Caba, Buenos Aires, Argentina

Local Institution - 0171; 🇯🇵 Yokohama, Kanagawa, Japan

Local Institution - 0052; 🇮🇹 Milano, Italy

Local Institution - 0073; 🇦🇺 Westmead, New South Wales, Australia

Local Institution - 0010; 🇩🇪 Muenchen, Germany

Local Institution - 0061; 🇧🇷 Sao Paulo, Brazil

Local Institution - 0023; 🇩🇪 Jena, Germany

Local Institution - 0066; 🇧🇷 Rio De Janeiro, Brazil

Local Institution - 0119; 🇧🇷 Ijui, RIO Grande DO SUL, Brazil

Local Institution - 0049; 🇦🇷 Cordoba, Argentina

Local Institution - 0047; 🇦🇷 Tucuman, Argentina

Local Institution - 0011; 🇩🇪 Tuebingen, Germany

Local Institution - 0146; 🇹🇷 Istanbul, Turkey

Local Institution - 0117; 🇩🇪 Essen, Germany

Local Institution - 0144; 🇪🇸 Santander, Spain

Local Institution - 0120; 🇪🇸 Madrid, Spain

Local Institution - 0124; 🇪🇸 Sevilla, Spain

Local Institution - 0082; 🇬🇷 Athens, Greece

Local Institution - 0033; 🇨🇿 Olomouc, Czechia

Local Institution - 0071; 🇮🇱 Petah Tikva, Israel

Local Institution - 0107; 🇹🇷 Ankara, Turkey

Local Institution - 0013; 🇩🇪 Aachen, Germany

Local Institution - 0014; 🇩🇪 Nuernberg, Germany

Local Institution - 0034; 🇨🇿 Hradec Kralove, Czechia

Local Institution - 0016; 🇩🇪 Bonn, Germany

Local Institution - 0169; 🇯🇵 Okayama-shi, Okayama, Japan

Local Institution - 0108; 🇲🇽 Zapopan, Jalisco, Mexico

Local Institution - 0140; 🇬🇧 Truro, United Kingdom

Local Institution - 0111; 🇬🇧 London, United Kingdom

Local Institution - 0109; 🇬🇧 Manchester, United Kingdom

Local Institution - 0133; 🇺🇸 Bakersfield, California, United States

Local Institution - 0093; 🇺🇸 Los Angeles, California, United States

Local Institution - 0091; 🇺🇸 Fort Wayne, Indiana, United States

Local Institution - 0113; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 0075; 🇺🇸 Dallas, Texas, United States

Local Institution - 0068; 🇺🇸 Houston, Texas, United States

Local Institution - 0009; 🇦🇺 Sydney, New South Wales, Australia

Local Institution - 0006; 🇦🇺 Herston, Queensland, Australia

Local Institution - 0080; 🇺🇸 San Antonio, Texas, United States

Local Institution - 0077; 🇺🇸 Daphne, Alabama, United States

Local Institution - 0036; 🇺🇸 Chicago, Illinois, United States

Local Institution - 0042; 🇺🇸 Zion, Illinois, United States

Local Institution - 0037; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 0040; 🇺🇸 Buffalo, New York, United States

Local Institution - 0135; 🇺🇸 Allentown, Pennsylvania, United States

Local Institution - 0131; 🇺🇸 Norfolk, Virginia, United States

Local Institution - 0008; 🇦🇺 Sydney, New South Wales, Australia

Local Institution - 0004; 🇦🇺 Elizabeth Vale, South Australia, Australia

Local Institution - 0054; 🇮🇹 Arezzo, Italy

Local Institution - 0157; 🇯🇵 Sapporo-shi, Hokkaido, Japan

Local Institution - 0159; 🇯🇵 Morioka, Iwate, Japan

Local Institution - 0150; 🇯🇵 Niigata-shi, Niigata, Japan

Local Institution - 0154; 🇯🇵 Osaka, Osaka-shi, Japan

Local Institution - 0065; 🇲🇽 Monterrey, Nuevo Leon, Mexico

Local Institution - 0115; 🇲🇽 Tlalpan, Distrito Federal, Mexico

Local Institution - 0063; 🇲🇽 Queretaro, Mexico

Local Institution - 0084; 🇵🇱 Biala Podlaska, Poland

Local Institution - 0096; 🇹🇷 Antalya, Turkey

Local Institution - 0007; 🇦🇺 Doubleview, Western Australia, Australia

Local Institution - 0056; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Local Institution - 0057; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Local Institution - 0060; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Local Institution - 0055; 🇮🇹 Napoli, Italy

Local Institution - 0053; 🇮🇹 Padova, Italy

Local Institution - 0051; 🇮🇹 Pavia, Italy

Local Institution - 0147; 🇮🇹 Pavia, Italy

Local Institution - 0172; 🇮🇹 Terni, Italy

Local Institution - 0139; 🇹🇷 Ankara, Turkey

Local Institution - 0094; 🇹🇷 Ankara, Turkey

Local Institution - 0097; 🇹🇷 Denizli, Turkey

Local Institution - 0095; 🇹🇷 Edirne, Turkey

Local Institution - 0123; 🇪🇸 Valencia, Spain

Local Institution - 0044; 🇺🇸 Goodyear, Arizona, United States

Local Institution - 0132; 🇺🇸 Tucson, Arizona, United States

Local Institution - 0050; 🇦🇷 Cordoba, Argentina

Local Institution - 0045; 🇨🇱 Santiago, Metropolitana, Chile

Local Institution - 0083; 🇬🇷 Thessaloniki, Greece

Local Institution - 0020; 🇷🇺 Moscow, Russian Federation

Local Institution - 0072; 🇮🇱 Haifa, Israel

Local Institution - 0164; 🇯🇵 Sapporo, Hokkaido, Japan

Local Institution - 0170; 🇯🇵 Osaka-shi, Osaka, Japan

Local Institution - 0022; 🇷🇴 Craiova, Romania

Local Institution - 0155; 🇯🇵 Hidaka-shi, Saitama, Japan

Local Institution - 0158; 🇯🇵 Bunkyo-ku, Tokyo, Japan

Local Institution - 0156; 🇯🇵 Aomori, Japan

Local Institution - 0165; 🇯🇵 Yamagata, Japan

Local Institution - 0064; 🇲🇽 Monterrey, Nuevo Leon, Mexico

Local Institution - 0130; 🇵🇱 Bydgoszcz, Poland

Local Institution - 0085; 🇵🇱 Gdansk, Poland

Local Institution - 0002; 🇦🇺 North Ryde, New South Wales, Australia

Local Institution - 0148; 🇯🇵 Akita-shi, Akita, Japan

Local Institution - 0168; 🇯🇵 Kobe, Hyogo, Japan

Local Institution - 0167; 🇯🇵 Chiba, Japan

Local Institution - 0161; 🇯🇵 Fukuoka, Japan

Local Institution - 0105; 🇺🇸 Nashville, Tennessee, United States

Local Institution - 0048; 🇦🇷 Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina

Local Institution - 0114; 🇦🇷 Viedma, RIO Negro, Argentina

Local Institution - 0070; 🇮🇱 Kfar Saba, Israel

Local Institution - 0102; 🇺🇸 Las Vegas, Nevada, United States

Local Institution - 0138; 🇦🇷 Caba, Argentina

Local Institution - 0069; 🇮🇱 Ramat Gan, Israel

Local Institution - 0160; 🇯🇵 Osakasayamashi, Osaka, Japan

Local Institution - 0153; 🇯🇵 Tokushima-shi, Tokushima, Japan

Local Institution - 0149; 🇯🇵 Tokyo, Japan

Local Institution - 0173; 🇯🇵 Minato-ku, Tokyo, Japan

Local Institution - 0166; 🇯🇵 Yokohama, Kanagawa, Japan

Local Institution - 0163; 🇯🇵 Suita-shi, Osaka, Japan

Local Institution - 0152; 🇯🇵 Adachi-ku, Tokyo, Japan

Local Institution - 0151; 🇯🇵 Bunkyo-ku, Tokyo, Japan

Local Institution - 0162; 🇯🇵 Nagasaki, Japan

Local Institution - 0116; 🇲🇽 Mexico, Distrito Federal, Mexico

Local Institution - 0021; 🇷🇴 Cluj-Napoca, Romania

Local Institution - 0099; 🇷🇺 Saint-Petersburg, Russian Federation

Local Institution - 0062; 🇲🇽 Ciudad de Mexico, Distrito Federal, Mexico

Local Institution - 0143; 🇲🇽 Monterrey, Nuevo LEON, Mexico

Local Institution - 0136; 🇲🇽 Merida, Yucatan, Mexico

Local Institution - 0087; 🇺🇸 Wichita, Kansas, United States