Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
- Conditions
- Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT03937219
- Lead Sponsor
- Exelixis
- 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 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 855
- 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. Measurable disease must be outside the radiation field if radiation therapy was previously administered.
- Karnofsky Performance Status (KPS) ≥ 70%.
- Adequate organ and marrow function.
-
Prior systemic anticancer therapy for unresectable locally advanced or metastatic RCC including investigational agents.
-
Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
-
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and stable for at least 4 weeks prior to randomization.
-
Concomitant anticoagulation with oral anticoagulants or platelet inhibitors.
-
Administration of a live, attenuated vaccine within 30 days prior to randomization.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Arm Nivolumab Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab Experimental Arm Cabozantinib Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab Control Arm Cabozantinib-matched placebo Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab Experimental Arm Ipilimumab Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab Experimental Arm Nivolumab Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab Control Arm Ipilimumab Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
- Primary Outcome Measures
Name Time Method Duration of Progression-Free Survival (PFS) per RECIST 1.1 as determined by blinded independent radiology committee (BIRC) Up to 23 months after first subject randomized
- Secondary Outcome Measures
Name Time Method Duration of Overall Survival (OS) Up to 69 months after first subject randomized
Trial Locations
- Locations (159)
Exelixis Clinical Site #29
🇺🇸Boca Raton, Florida, United States
Exelixis Clinical Site #58A
🇺🇸Baltimore, Maryland, United States
Exelixis Clinical Site #12
🇺🇸Pittsburgh, Pennsylvania, United States
Exelixis Clinical Site #134
🇲🇽Monterrey, Nuevo León, Mexico
Exelixis Clinical Site #95
🇺🇸Chicago, Illinois, United States
Exelixis Clinical Site #7C
🇺🇸Boston, Massachusetts, United States
Exelixis Clinical Site #57
🇺🇸Seattle, Washington, United States
Exelixis Clinical Site #163
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Exelixis Clinical Site #167
🇲🇽León, Guanajuato, Mexico
Exelixis Clinical Site #126
🇦🇹Vienna, Austria
Exelixis Clinical Site #111
🇭🇰Tuen Mun, Hong Kong
Exelixis Clinical Site #88
🇮🇱Be'er Sheva, Israel
Exelixis Clinical Site #84
🇮🇱Jerusalem, Israel
Exelixis Clinical Site #39
🇭🇺Budapest, Hungary
Exelixis Clinical Site #23
🇦🇺Box Hill, Victoria, Australia
Exelixis Clinical Site #131
🇲🇽Querétaro, Mexico
Exelixis Clinical Site #162
🇧🇷São José Do Rio Preto, São Paulo, Brazil
Exelixis Clinical Site #161
🇲🇽Querétaro, Mexico
Exelixis Clinical Site #127
🇩🇪Heidelberg, Baden-Württemberg, Germany
Exelixis Clinical Site #98
🇦🇹Wiener Neustadt, Niederösterreich, Austria
Exelixis Clinical Site #75
🇦🇹Salzburg, Austria
Exelixis Clincal Site #129
🇮🇱Ramat Gan, Israel
Exelixis Clinical Site #123
🇲🇽Aguascalientes, Ags, Mexico
Exelixis Clinical Site #44
🇺🇸Miami, Florida, United States
Exelixis Clinical Site #10
🇺🇸Nashville, Tennessee, United States
Exelixis Clinical Site #38
🇺🇸Nashville, Tennessee, United States
Exelixis Clinical Site #2
🇺🇸Omaha, Nebraska, United States
Exelixis Clinical Site #116
🇺🇸La Jolla, California, United States
Exelixis Clinical Site #69
🇺🇸Scarborough, Maine, United States
Exelixis Clinical Site #6
🇺🇸Burlington, Massachusetts, United States
Exelixis Clinical Site #8
🇺🇸New York, New York, United States
Exelixis Clinical Site #101
🇺🇸Charlotte, North Carolina, United States
Exelixis Clinical Site #35
🇦🇺Kogarah, New South Wales, Australia
Exelixis Clinical Site #27
🇦🇺North Ryde, New South Wales, Australia
Exelixis Clinical Site #17
🇦🇺South Brisbane, Queensland, Australia
Exelixis Clinical Site #14
🇦🇺Woolloongabba, Queensland, Australia
Exelixis Clinical Site #18
🇦🇺Adelaide, South Australia, Australia
Exelixis Clinical Site #26
🇦🇺Subiaco, Western Australia, Australia
Exelixis Clinical Site #112
🇧🇪Brussels, Belgium
Exelixis Clinical Site #146
🇧🇪Hasselt, Belgium
Exelixis Clinical Site #140
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Exelixis Clinical Site #25
🇨🇦Toronto, Ontario, Canada
Exelixis Clinical Site #22
🇨🇦Calgary, Alberta, Canada
Exelixis Clinical Site #50
🇫🇮Helsinki, Finland
Exelixis Clinical Site #114
🇨🇿Praha 4, Czechia
Exelixis Clinical Site #113
🇨🇦Montréal, Quebec, Canada
Exelixis Clinical Site #91
🇨🇱Santiago, Chile
Exelixis Clinical Site #89
🇨🇿Králová, Czechia
Exelixis Clinical Site #118
🇨🇿Praha 5, Czechia
Exelixis Clinical Site #71
🇫🇷Le Mans, France
Exelixis Clinical Site #80
🇫🇷Montpellier Cedex 5, France
Exelixis Clinical Site #78
🇫🇷Lyon Cedex 8, France
Exelixis Clinical Site #65
🇫🇷Reims Cedex, France
Exelixis Clinical Site #128
🇫🇷Strasbourg, France
Exelixis Clinical Site #90
🇫🇷Strasbourg, France
Exelixis Clinical Site #67
🇫🇷Vandœuvre-lès-Nancy, France
Exelixis Clinical Site #117
🇩🇪Frankfurt am main, Hessen, Germany
Exelixis Clinical Site #164
🇩🇪Mainz, Rheinland-Pfalz, Germany
Exelixis Clinical Site #124
🇩🇪Dresden, Germany
Exelixis Clinical Site #51
🇭🇺Pécs, Hungary
Exelixis Clinical Site #81
🇮🇱Haifa, Israel
Exelixis Clinical Site #121
🇮🇱Kfar Saba, Israel
Exelixis Clinical Site #60
🇮🇹Modena, Italy
Exelixis Clinical Site #104
🇮🇹Perugia, Italy
Exelixis Clinical Site #61
🇮🇹Padova, Italy
Exelixis Clinical Site #68
🇮🇹Terni, Italy
Exelixis Clinical Site #147
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Exelixis Clinical Site #143
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #152
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #151
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #169
🇲🇽Zapopan, Jalisco, Mexico
Exelixis Clinical Site #132
🇲🇽Oaxaca de Juarez, Oaxaca, Mexico
Exelixis Clinical Site #144
🇳🇱Amsterdam, Netherlands
Exelixis Clinical Site #31
🇵🇱Biała Podlaska, Poland
Exelixis Clinical Site #62
🇵🇱Bydgoszcz, Poland
Exelixis Clinical Site #135
🇵🇱Gdańsk, Poland
Exelixis Clinical Site #99
🇵🇱Otwock, Poland
Exelixis Clinical Site #83
🇵🇱Poznań, Poland
Exelixis Clinical Site #43
🇪🇸Barcelona, Spain
Exelixis Clinical Site #40
🇸🇬Singapore, Singapore
Exelixis Clinical Site #49
🇪🇸Córdoba, Spain
Exelixis Clinical Site #53
🇪🇸Santiago De Compostela, Coruña, Spain
Exelixis Clinical Site #36
🇪🇸Barcelona, Spain
Exelixis Clinical Site #55
🇪🇸Madrid, Spain
Exelixis Clinical Site #94
🇪🇸Madrid, Spain
Exelixis Clinical Site #20
🇪🇸Madrid, Spain
Exelixis Clinical Site #34
🇪🇸Madrid, Spain
Exelixis Clinical Site #96
🇪🇸Oviedo, Spain
Exelixis Clinical Site #74
🇪🇸Valencia, Spain
Exelixis Clinical Site #172
🇬🇧London, United Kingdom
Exelixis Clinical Site #93
🇬🇧Glasgow, United Kingdom
Exelixis Clinical Site #72
🇬🇧Cambridge, United Kingdom
Exelixis Clinical Site #30
🇬🇧London, United Kingdom
Exelixis Clinical Site #92
🇬🇧Manchester, United Kingdom
Exelixis Clinical Site #7B
🇺🇸Boston, Massachusetts, United States
Exelixis Clinical Site #59
🇮🇹Pavia, Italy
Exelixis Clinical Site #166
🇺🇸Orange, California, United States
Exelixis Clinical Site #3
🇺🇸Atlanta, Georgia, United States
Exelixis Clinical Site #7A
🇺🇸Boston, Massachusetts, United States
Exelixis Clinical Site #15
🇺🇸Detroit, Michigan, United States
Exelixis Clinical Site #4
🇺🇸Saint Louis, Missouri, United States
Exelixis Clinical Site #19
🇺🇸Syracuse, New York, United States
Exelixis Clinical Site #159
🇺🇸New York, New York, United States
Exelixis Clinical Site #107
🇺🇸Portland, Oregon, United States
Exelixis Clinical Site #5
🇺🇸Myrtle Beach, South Carolina, United States
Exelixis Clinical Site #1
🇺🇸Spokane, Washington, United States
Exelixis Clinical Site #13
🇺🇸Madison, Wisconsin, United States
Exelixis Clinical Site #64
🇺🇸Fairfax, Virginia, United States
Exelixis Clinical Site #109
🇦🇷Rosario, Santa Fe, Argentina
Exelixis Clinical Site #153
🇦🇷Pilar, Provincia De Buenos Aires, Argentina
Exelixis Clinical Site #73
🇦🇷San Miguel De Tucumán, Tucumán, Argentina
Exelixis Clinical Site #63
🇦🇷Caba, Argentina
Exelixis Clinical Site #110
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Exelixis Clinical Site #54
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Exelixis Clinical Site #120
🇦🇷Córdoba, Argentina
Exelixis Clinical Site #32
🇦🇺Albury, New South Wales, Australia
Exelixis Clinical Site #33
🇦🇺Sydney, New South Wales, Australia
Exelixis Clinical Site #9
🇦🇺Ballarat, Victoria, Australia
Exelixis Clinical Site #11
🇦🇺North Adelaide, South Australia, Australia
Exelixis Clinical Site #76
🇦🇹Linz, Oberösterreich, Austria
Exelixis Clinical Site #155
🇧🇷Curitiba, Parana, Brazil
Exelixis Clinical Site #154
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Exelixis Clinical Site #158
🇧🇷Porto Alegre, RS, Brazil
Exelixis Clinical Site #168
🇧🇷Barretos, São Paulo, Brazil
Exelixis Clinical Site #105
🇨🇦Winnipeg, Manitoba, Canada
Exelixis Clinical Site #46
🇨🇦Ottawa, Ontario, Canada
Exelixis Clinical Site #119
🇧🇷São Paulo, Brazil
Exelixis Clinical Site #141
🇧🇷São Paulo, Brazil
Exelixis Clinical Site #85
🇨🇱Temuco, Región De La Araucanía (IX), Chile
Exelixis Clinical Site #56
🇫🇮Tampere, Finland
Exelixis Clinical Site #100
🇨🇱Santiago, Chile
Exelixis Clinical Site #150
🇫🇷Paris, France
Exelixis Clinical Site #86
🇫🇷Bordeaux, France
Exelixis Clinical Site #52
🇫🇮Turku, Finland
Exelixis Clinical Site #66
🇫🇷Nice Cedex 2, France
Exelixis Clinical Site #42
🇫🇷Toulouse Cedex 9, France
Exelixis Clinical Site #125
🇫🇷Rennes, France
Exelixis Clinical Site #37
🇫🇷Villejuif, France
Exelixis Clinical Site #139
🇩🇪Münster, Nordrhein-Westfalen, Germany
Exelixis Clinical Site #115
🇩🇪Tübingen, Baden-Württemberg, Germany
Exelixis Clinical Site #171
🇩🇪Münster, Nordrhein-Westfalen, Germany
Exelixis Clinical Site #137
🇩🇪Jena, Thüringen, Germany
Exelixis Clinical Site #47
🇮🇹Arezzo, Italy
Exelixis Clinical Site #70
🇮🇹Faenza, Ravenna, Italy
Exelixis Clinical Site #41
🇮🇹Meldola, Forli - Cesena, Italy
Exelixis Clinical Site #97
🇮🇱Petach Tikva, Israel
Exelixis Clinical Site #160
🇲🇽Ciudad de México, Mexico
Exelixis Clinical Site #122
🇳🇿Hamilton, Waikato, New Zealand
Exelixis Clinical Site #149
🇳🇱Rotterdam, Netherlands
Exelixis Clinical Site #148
🇳🇿Newtown, Wellington, New Zealand
Exelixis Clinical Site #77
🇸🇬Singapore, Singapore
Exelixis Clinical Site #45
🇪🇸Pamplona, Navarra, Spain
Exelixis Clinical Site #138
🇨🇳Taipei, Taiwan
Exelixis Clinical Site #142
🇨🇳Taichung, Taiwan
Exelixis Clinical Site #173
🇨🇳Taoyuan, Taiwan
Exelixis Clinical Site #24
🇺🇸Kansas City, Missouri, United States
Exelixis Clinical Site #102
🇺🇸Charleston, South Carolina, United States
Exelixis Clinical Site #136
🇭🇰Shatin, Hong Kong
Exelixis Clinical Site #28
🇭🇰Hong Kong, Hong Kong