Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03937219
Recruitment Status : Recruiting
First Posted : May 3, 2019
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Exelixis

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Cabozantinib Biological: Nivolumab Biological: Ipilimumab Drug: Cabozantinib-matched placebo Phase 3

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 676 participants
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
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
Actual Study Start Date : June 25, 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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-matched placebo + 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03937219


Contacts
Layout table for location contacts
Contact: Exelixis Clinical Trials 1-888-EXELIXIS (888-393-5494) druginfo@exelixis.com
Contact: Backup or International 650-837-7400

  Show 168 Study Locations
Sponsors and Collaborators
Exelixis
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for additonal information
Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT03937219     History of Changes
Other Study ID Numbers: XL184-313
First Posted: May 3, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Exelixis:
renal
cancer
carcinoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
 Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents