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Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313)

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ClinicalTrials.gov Identifier: NCT03937219
Recruitment Status : Recruiting
First Posted : May 3, 2019
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
Exelixis

Tracking Information
First Submitted Date  ICMJE May 2, 2019
First Posted Date  ICMJE May 3, 2019
Last Update Posted Date March 25, 2020
Actual Study Start Date  ICMJE June 25, 2019
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
Duration of Overall Survival (OS) [ Time Frame: Up to 58 months after first subject randomized ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
Official Title  ICMJE 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
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 180 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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).
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Carcinoma
Intervention  ICMJE
  • 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
  • Drug: Cabozantinib-matched placebo
    Specified dose on specified days.
Study Arms  ICMJE
  • Experimental: Experimental Arm
    Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
    Interventions:
    • Drug: Cabozantinib
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Active Comparator: Control Arm
    Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
    • Drug: Cabozantinib-matched placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 2, 2019)
676
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 anticancer 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 lesions invading major pulmonary blood vessels.
  • Other clinically significant disorders such as:

    i. Autoimmune disease that has been symptomatic or required treatment within the past two years from the date of randomization.

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 where there is clinical or radiographic evidence of active myobacterial infection.

  • Major surgery (eg, nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Exelixis Clinical Trials 1-888-EXELIXIS (888-393-5494) druginfo@exelixis.com
Contact: Backup or International 650-837-7400
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Chile,   Czechia,   Finland,   France,   Germany,   Hong Kong,   Hungary,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   New Zealand,   Poland,   Singapore,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03937219
Other Study ID Numbers  ICMJE XL184-313
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Exelixis
Study Sponsor  ICMJE Exelixis
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Exelixis
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP