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 840 eligible subjects with intermediate- or poor-risk
advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio at
approximately 180 sites.
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
Interventions
Drug | Synonyms | Arms |
---|
Cabozantinib | Cabometyx, XL184 | Experimental Arm |
Nivolumab | Opdivo, BMS-936558 | Control Arm |
Ipilimumab | Yervoy, BMS-734016 | Control Arm |
Cabozantinib-matched placebo | | Control 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 840 eligible subjects with intermediate- or poor-risk
advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio 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).
Trial Arms
Name | Type | Description | Interventions |
---|
Experimental Arm | Experimental | Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab | - Cabozantinib
- Nivolumab
- Ipilimumab
|
Control Arm | Active Comparator | Cabozantinib-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 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:
- Autoimmune disease that has been symptomatic or required treatment within the
past two years from the date of randomization.
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg
daily prednisone equivalent) or other immunosuppressive medications within 14
days of randomization.
- 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.
- Known history of COVID-19 unless the subject has clinically recovered from the
disease at least 30 days prior to randomization.
- 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.
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 69 months after first subject randomized |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Exelixis |
Trial Keywords
Last Updated
April 1, 2021