Clinical Trials /

Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

NCT03937219

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. 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.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: XL184-313
  • NCT ID: NCT03937219

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
CabozantinibCabometyx, XL184Experimental Arm
NivolumabOpdivo, BMS-936558Experimental Arm
IpilimumabYervoy, BMS-734016Experimental Arm
Cabozantinib-matched placeboControl Arm

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Experimental ArmExperimentalCabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
  • Cabozantinib
  • Nivolumab
  • Ipilimumab
Control ArmActive ComparatorCabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
  • Nivolumab
  • Ipilimumab
  • Cabozantinib-matched placebo

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of Overall Survival (OS)
Time Frame:Up to 58 months after first subject randomized
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Exelixis

Trial Keywords

  • renal
  • cancer
  • carcinoma

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