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History of Changes for Study: NCT03937219
Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313)
Latest version (submitted March 8, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 2, 2019 None (earliest Version on record)
2 May 8, 2019 Arms and Interventions and Study Status
3 May 16, 2019 Contacts/Locations and Study Status
4 June 20, 2019 Contacts/Locations and Study Status
5 July 2, 2019 Recruitment Status, Study Status and Contacts/Locations
6 July 3, 2019 Contacts/Locations and Study Status
7 August 5, 2019 Contacts/Locations and Study Status
8 August 15, 2019 Study Status and Contacts/Locations
9 September 24, 2019 Contacts/Locations and Study Status
10 October 9, 2019 Contacts/Locations and Study Status
11 October 17, 2019 Contacts/Locations and Study Status
12 December 9, 2019 Contacts/Locations and Study Status
13 December 13, 2019 Contacts/Locations and Study Status
14 January 14, 2020 Contacts/Locations and Study Status
15 February 14, 2020 Contacts/Locations, Study Status, Eligibility and Study Description
16 March 4, 2020 Contacts/Locations and Study Status
17 March 17, 2020 Contacts/Locations and Study Status
18 March 24, 2020 Contacts/Locations and Study Status
19 April 14, 2020 Contacts/Locations and Study Status
20 June 2, 2020 Contacts/Locations and Study Status
21 June 16, 2020 Contacts/Locations and Study Status
22 July 6, 2020 Contacts/Locations and Study Status
23 August 14, 2020 Contacts/Locations and Study Status
24 August 26, 2020 Contacts/Locations and Study Status
25 October 29, 2020 Contacts/Locations and Study Status
26 November 4, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Design
27 November 9, 2020 Study Design and Study Status
28 November 11, 2020 Contacts/Locations and Study Status
29 November 18, 2020 Study Design and Study Status
30 December 2, 2020 Study Status and Study Design
31 December 3, 2020 Study Design and Study Status
32 December 19, 2020 Recruitment Status, Study Status, Contacts/Locations, Study Design, Eligibility, Outcome Measures and Study Description
33 February 8, 2021 Study Status and Contacts/Locations
34 March 30, 2021 Recruitment Status, Study Status and Contacts/Locations
35 March 8, 2022 Study Status
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Study NCT03937219
Submitted Date:  May 2, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: XL184-313
Brief Title: Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313)
Official Title: A Randomized, Double-Blind, Controlled Phase 3 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab Versus Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma of Intermediate or Poor Risk
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2019
Overall Status: Not yet recruiting
Study Start: June 2019
Primary Completion: November 2021 [Anticipated]
Study Completion: June 2024 [Anticipated]
First Submitted: May 2, 2019
First Submitted that
Met QC Criteria:
May 2, 2019
First Posted: May 3, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
May 2, 2019
Last Update Posted: May 3, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Exelixis
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. Approximately 676 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio (~338 per treatment arm) at approximately 150 sites.
Detailed Description: This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. The primary objective of this study is to evaluate the effect of cabozantinib in combination with nivolumab and ipilimumab ("triplet") on the duration of progression-free survival (PFS) versus nivolumab and ipilimumab. A secondary objective is to evaluate the effect of triplet combination on the duration of overall survival (OS).
Open or close this module Conditions
Conditions: Renal Cell Carcinoma
Keywords: renal
cancer
carcinoma
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Approximately 676 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio (~338 per treatment arm).
Number of Arms: 2
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 676 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Experimental Arm
Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
Drug: Cabozantinib
Specified dose on specified days.
Other Names:
  • Cabometyx
  • XL184
Biological: Nivolumab
Specified dose on specified days.
Other Names:
  • Opdivo
  • BMS-936558
Biological: Ipilimumab
Specified dose on specified days.
Other Names:
  • Yervoy
  • BMS-734016
Active Comparator: Control Arm
Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
Biological: Nivolumab
Specified dose on specified days.
Other Names:
  • Opdivo
  • BMS-936558
Biological: Ipilimumab
Specified dose on specified days.
Other Names:
  • Yervoy
  • BMS-734016
Drug: Cabozantinib-matched placebo
Specified dose on specified days.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Duration of Progression-Free Survival (PFS) per RECIST 1.1 as determined by blinded independent radiology committee (BIRC)
[ Time Frame: Up to 23 months after first subject randomized ]

Secondary Outcome Measures:
1. Duration of Overall Survival (OS)
[ Time Frame: Up to 58 months after first subject randomized ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.
  • Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria.
  • Measurable disease per RECIST 1.1 as determined by the Investigator.
  • Karnofsky Performance Status (KPS) ≥ 70%.
  • Adequate organ and marrow function.

Exclusion Criteria:

  • Prior systemic therapy for unresectable locally advanced or metastatic RCC including investigational agents.
  • Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesion invading major pulmonary blood vessels.
  • Other clinically significant disorders such as:

    i. Any active, known or suspected autoimmune disease. ii. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. iii. Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection.

  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Prior laparoscopic nephrectomy within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major surgery or minor surgery before randomization.
  • Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
Open or close this module Contacts/Locations
Central Contact Person: Exelixis Clinical Trials
Telephone: 1-888-EXELIXIS (888-393-5494)
Email: druginfo@exelixis.com
Central Contact Backup: Backup or International
Telephone: 650-837-7400
Locations: United States, California
Exelixis Clinical Site - La Jolla
La Jolla, California, United States, 92093
United States, Florida
Exelixis Clinical Site - Miami
Miami, Florida, United States, 33176
United States, Georgia
Exelixis Clinical Site - Atlanta
Atlanta, Georgia, United States, 30318
United States, Illinois
Exelixis Clinical Site - Chicago
Chicago, Illinois, United States, 60612
United States, Massachusetts
Exelixis Clinical Site - Boston #2
Boston, Massachusetts, United States, 02114
Exelixis Clinical Site - Boston #1
Boston, Massachusetts, United States, 02215
Exelixis Clinical Site - Boston #3
Boston, Massachusetts, United States, 02215
Exelixis Clinical Site - Burlington
Burlington, Massachusetts, United States, 01805
United States, Michigan
Exelixis Clinical Site - Detroit
Detroit, Michigan, United States, 48201
United States, Missouri
Exelixis Clinical Site - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Exelixis Clinical Site - Omaha
Omaha, Nebraska, United States, 68130
United States, New York
Exelixis Clinical Site - New York
New York, New York, United States, 10065
Exelixis Clinical Site - Syracuse
Syracuse, New York, United States, 13210
United States, North Carolina
Exelixis Clinical Site - Charlotte
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
Exelixis Clinical Site - Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Exelixis Clinical Site - Charleston
Charleston, South Carolina, United States, 29425
Exelixis Clinical Site - Myrtle Beach
Myrtle Beach, South Carolina, United States, 29572
United States, Tennessee
Exelixis Clinical Site - Nashville
Nashville, Tennessee, United States, 37232
United States, Washington
Exelixis Clinical Site - Seattle
Seattle, Washington, United States, 98109
Exelixis Clinical Site - Spokane
Spokane, Washington, United States, 99208
United States, Wisconsin
Exelixis Clinical Site - Madison
Madison, Wisconsin, United States, 53792
Argentina
Exelixis Clinical Site - Capital Federal
Capital Federal, Argentina
Exelixis Clinical Site - Rosario
Rosario, Argentina
Exelixis Clinical Site - San Miguel De Tucumán
San Miguel De Tucumán, Argentina
Australia
Exelixis Clinical Site - Adelaide
Adelaide, Australia
Exelixis Clinical Site - Albury
Albury, Australia
Exelixis Clinical Site - Ballarat
Ballarat, Australia
Exelixis Clinical Site - Box Hill
Box Hill, Australia
Exelixis Clinical Site - Darlinghurst
Darlinghurst, Australia
Exelixis Clinical Site - Elizabeth Vale #1
Elizabeth Vale, Australia
Exelixis Clinical Site - Elizabeth Vale #2
Elizabeth Vale, Australia
Exelixis Clinical Site - Kogarah
Kogarah, Australia
Exelixis Clinical Site - Port Macquarie
Port Macquarie, Australia
Exelixis Clinical Site - Randwick
Randwick, Australia
Exelixis Clinical Site - Saint Leonards
Saint Leonards, Australia
Exelixis Clinical Site - South Brisbane
South Brisbane, Australia
Exelixis Clinical Site - Subiaco
Subiaco, Australia
Exelixis Clinical Site - Sydney
Sydney, Australia
Exelixis Clinical Site - Woolloongabba
Woolloongabba, Australia
Brazil
Exelixis Clinical Site - Belo Horizonte
Belo Horizonte, Brazil
Exelixis Clinical Site - Porto Alegre #1
Porto Alegre, Brazil
Exelixis Clinical Site - Porto Alegre #2
Porto Alegre, Brazil
Exelixis Clinical Site - São José Do Rio Preto
São José Do Rio Preto, Brazil
Exelixis Clinical Site - São Paulo
São Paulo, Brazil
Canada, Ontario
Exelixis Clinical Site - Toronto
Toronto, Ontario, Canada
France
Exelixis Clinical Site - Besançon
Besançon, France
Exelixis Clinical Site - Le Mans
Le Mans, France
Exelixis Clinical Site - Lyon
Lyon, France
Exelixis Clinical Site - Nantes
Nantes, France
Exelixis Clinical Site - Nice
Nice, France
Exelixis Clinical Site - Reims
Reims, France
Exelixis Clinical Site - Rennes
Rennes, France
Exelixis Clinical Site - Strasbourg
Strasbourg, France
Exelixis Clinical Site - Toulouse
Toulouse, France
Exelixis Clinical Site - Vandœuvre-lès-Nancy
Vandœuvre-lès-Nancy, France
Germany
Exelixis Clinical Site - Jena
Jena, Germany
Exelixis Clinical Site - Luebeck
Luebeck, Germany
Hong Kong
Exelixis Clinical Site - Hong Kong
Hong Kong, Hong Kong
Exelixis Clinical Site - Tuen Mun
Tuen Mun, Hong Kong
Hungary
Exelixis Clinical Site - Budapest
Budapest, Hungary
Israel
Exelixis Clinical Site - Haifa
Haifa, Israel
Exelixis Clinical Site - Kfar Saba
Kfar Saba, Israel
Exelixis Clinical Site - Petah Tikva
Petah Tikva, Israel
Italy
Exelixis Clinical Site - Arezzo
Arezzo, Italy
Exelixis Clinical Site - Padova
Padova, Italy
Exelixis Clinical Site - Terni
Terni, Italy
Mexico
Exelixis Clinical Site - Mexico City
Mexico City, Mexico
Poland
Exelixis Clinical Site - Bydgoszcz
Bydgoszcz, Poland
Spain
Exelixis Clinical Site - Barcelona
Barcelona, Spain
Exelixis Clinical Site - Córdoba
Córdoba, Spain
Exelixis Clinical Site - Madrid #1
Madrid, Spain
Exelixis Clinical Site - Madrid #2
Madrid, Spain
Exelixis Clinical Site - Madrid #3
Madrid, Spain
Exelixis Clinical Site - Oviedo
Oviedo, Spain
Exelixis Clinical Site - Santiago De Compostela
Santiago De Compostela, Spain
Exelixis Clinical Site - Valencia
Valencia, Spain
United Kingdom
Exelixis Clinical Site - Bristol
Bristol, United Kingdom
Exelixis Clinical Site - Glasgow
Glasgow, United Kingdom
Exelixis Clinical Site - London
London, United Kingdom
Exelixis Clinical Site - Swansea
Swansea, United Kingdom
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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