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

Sponsor
Exelixis (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03937219
Collaborator
(none)
840
Enrollment
167
Locations
2
Arms
68.2
Anticipated Duration (Months)
5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • 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

Study Type:
Interventional
Anticipated Enrollment :
840 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio.Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio.
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 :
Jun 25, 2019
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Mar 1, 2025

Arms and Interventions

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

    Primary Outcome Measures

    1. 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

    1. Duration of Overall Survival (OS) [Up to 69 months after first subject randomized]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Exelixis Clinical Site #116 La Jolla California United States 92093
    2 Exelixis Clinical Site #166 Orange California United States 92868-3201
    3 Exelixis Clinical Site #58B Washington District of Columbia United States 20016
    4 Exelixis Clinical Site #29 Boca Raton Florida United States 33486
    5 Exelixis Clinical Site #44 Miami Florida United States 33176
    6 Exelixis Clinical Site #3 Atlanta Georgia United States 30318
    7 Exelixis Clinical Site #95 Chicago Illinois United States 60612
    8 Exelixis Clinical Site #69 Scarborough Maine United States 04074
    9 Exelixis Clinical Site #58A Baltimore Maryland United States 21287
    10 Exelixis Clinical Site #7B Boston Massachusetts United States 02114
    11 Exelixis Clinical Site #7A Boston Massachusetts United States 02215
    12 Exelixis Clinical Site #7C Boston Massachusetts United States 02215
    13 Exelixis Clinical Site #6 Burlington Massachusetts United States 01805
    14 Exelixis Clinical Site #15 Detroit Michigan United States 48201
    15 Exelixis Clinical Site #24 Kansas City Missouri United States 64132
    16 Exelixis Clinical Site #4 Saint Louis Missouri United States 63110
    17 Exelixis Clinical Site #2 Omaha Nebraska United States 68130
    18 Exelixis Clinical Site #159 New York New York United States 10032
    19 Exelixis Clinical Site #8 New York New York United States 10065
    20 Exelixis Clinical Site #19 Syracuse New York United States 13210
    21 Exelixis Clinical Site #101 Charlotte North Carolina United States 28204
    22 Exelixis Clinical Site #107 Portland Oregon United States 97239
    23 Exelixis Clinical Site #12 Pittsburgh Pennsylvania United States 15232
    24 Exelixis Clinical Site #102 Charleston South Carolina United States 29425
    25 Exelixis Clinical Site #5 Myrtle Beach South Carolina United States 29572
    26 Exelixis Clinical Site #10 Nashville Tennessee United States 37203
    27 Exelixis Clinical Site #38 Nashville Tennessee United States 37232
    28 Exelixis Clinical Site #64 Fairfax Virginia United States 22031
    29 Exelixis Clinical Site #57 Seattle Washington United States 98109
    30 Exelixis Clinical Site #1 Spokane Washington United States 99208
    31 Exelixis Clinical Site #13 Madison Wisconsin United States 53792
    32 Exelixis Clinical Site #153 Pilar Provincia De Buenos Aires Argentina B1629ODT
    33 Exelixis Clinical Site #109 Rosario Santa Fe Argentina S2000KZE
    34 Exelixis Clinical Site #73 San Miguel De Tucumán Tucumán Argentina T4000
    35 Exelixis Clinical Site #63 Caba Argentina C1120AAT
    36 Exelixis Clinical Site #54 Ciudad Autonoma de Buenos Aires Argentina C1125ABD
    37 Exelixis Clinical Site #110 Ciudad Autonoma de Buenos Aire Argentina C1426ANZ
    38 Exelixis Clinical Site #120 Córdoba Argentina X5004
    39 Exelixis Clinical Site #32 Albury New South Wales Australia 2640
    40 Exelixis Clinical Site #35 Kogarah New South Wales Australia 2217
    41 Exelixis Clinical Site #27 North Ryde New South Wales Australia 2109
    42 Exelixis Clinical Site #21 Randwick New South Wales Australia 2031
    43 Exelixis Clinical Site #33 Sydney New South Wales Australia 2065
    44 Exelixis Clinical Site #17 South Brisbane Queensland Australia 4101
    45 Exelixis Clinical Site #14 Woolloongabba Queensland Australia 4102
    46 Exelixis Clinical Site #18 Adelaide South Australia Australia 5000
    47 Exelixis Clinical Site #11 North Adelaide South Australia Australia 5006
    48 Exelixis Clinical Site #9 Ballarat Victoria Australia 3350
    49 Exelixis Clinical Site #23 Box Hill Victoria Australia 3128
    50 Exelixis Clinical Site #26 Subiaco Western Australia Australia 6008
    51 Exelixis Clinical Site #98 Wiener Neustadt Niederösterreich Austria 2700
    52 Exelixis Clinical Site #76 Linz Oberösterreich Austria 4020
    53 Exelixis Clinical Site #103 Linz Oberösterreich Austria 4021
    54 Exelixis Clinical Site #75 Salzburg Austria 5020
    55 Exelixis Clinical Site #126 Vienna Austria 1090
    56 Exelixis Clinical Site #112 Brussels Belgium 1000
    57 Exelixis Clinical Site #146 Hasselt Belgium 3500
    58 Exelixis Clinical Site #154 Belo Horizonte Minas Gerais Brazil 30130-090
    59 Exelixis Clinical Site #155 Curitiba Parana Brazil 80530-010
    60 Exelixis Clinical Site #140 Porto Alegre Rio Grande Do Sul Brazil 90110-270
    61 Exelixis Clinical Site #163 Porto Alegre Rio Grande Do Sul Brazil 90610-000
    62 Exelixis Clinical Site #158 Porto Alegre RS Brazil 90050-170
    63 Exelixis Clinical Site #168 Barretos São Paulo Brazil 14784-400
    64 Exelixis Clinical Site #162 São José Do Rio Preto São Paulo Brazil 15090-000
    65 Exelixis Clinical Site #119 São Paulo Brazil 01323-001
    66 Exelixis Clinical Site #141 São Paulo Brazil 01327-001
    67 Exelixis Clinical Site #22 Calgary Alberta Canada T2N 4N2
    68 Exelixis Clinical Site #105 Winnipeg Manitoba Canada R3E 0V9
    69 Exelixis Clinical Site #46 Ottawa Ontario Canada K1H 8L6
    70 Exelixis Clinical Site #25 Toronto Ontario Canada M4N 3M5
    71 Exelixis Clinical Site #113 Montréal Quebec Canada H3T 1E2
    72 Exelixis Clinical Site #85 Temuco Región De La Araucanía (IX) Chile 4810561
    73 Exelixis Clinical Site #91 Santiago Chile 7500921
    74 Exelixis Clinical Site #100 Santiago Chile 8420383
    75 Exelixis Clinical Site #89 Králová Czechia 50005
    76 Exelixis Clinical Site #114 Praha 4 Czechia 140 59
    77 Exelixis Clinical Site #118 Praha 5 Czechia 150 06
    78 Exelixis Clinical Site #50 Helsinki Finland 00029
    79 Exelixis Clinical Site #56 Tampere Finland 33520
    80 Exelixis Clinical Site #52 Turku Finland 20520
    81 Exelixis Clinical Site #87 Besançon France 25030
    82 Exelixis Clinical Site #86 Bordeaux France 33075
    83 Exelixis Clinical Site #71 Le Mans France 72000
    84 Exelixis Clinical Site #78 Lyon Cedex 8 France 69373
    85 Exelixis Clinical Site #80 Montpellier Cedex 5 France 34295
    86 Exelixis Clinical Site #66 Nice Cedex 2 France 06189
    87 Exelixis Clinical Site #150 Paris France 75015
    88 Exelixis Clinical Site #65 Reims Cedex France 51726
    89 Exelixis Clinical Site #125 Rennes France 35042
    90 Exelixis Clinical Site #128 Strasbourg France 67000
    91 Exelixis Clinical Site #90 Strasbourg France 67200
    92 Exelixis Clinical Site #42 Toulouse Cedex 9 France 31059
    93 Exelixis Clinical Site #67 Vandœuvre-lès-Nancy France 54519
    94 Exelixis Clinical Site #37 Villejuif France 94800
    95 Exelixis Clinical Site #127 Heidelberg Baden-Württemberg Germany 69120
    96 Exelixis Clinical Site #115 Tübingen Baden-Württemberg Germany 72076
    97 Exelixis Clinical Site #117 Frankfurt am main Hessen Germany 60596
    98 Exelixis Clinical Site #139 Münster Nordrhein-Westfalen Germany 48149
    99 Exelixis Clinical Site #171 Münster Nordrhein-Westfalen Germany 90419
    100 Exelixis Clinical Site #164 Mainz Rheinland-Pfalz Germany 55131
    101 Exelixis Clinical Site #137 Jena Thüringen Germany 077477
    102 Exelixis Clinical Site #124 Dresden Germany 01307
    103 Exelixis Clinical Site #28 Hong Kong Hong Kong
    104 Exelixis Clinical Site #136 Shatin Hong Kong
    105 Exelixis Clinical Site #111 Tuen Mun Hong Kong
    106 Exelixis Clinical Site #39 Budapest Hungary 1122
    107 Exelixis Clinical Site #51 Pécs Hungary 7624
    108 Exelixis Clinical Site #88 Be'er Sheva Israel 84101
    109 Exelixis Clinical Site #81 Haifa Israel 3109601
    110 Exelixis Clinical Site #84 Jerusalem Israel 9112001
    111 Exelixis Clinical Site #121 Kfar Saba Israel 4428164
    112 Exelixis Clinical Site #97 Petach Tikva Israel 49100
    113 Exelixis Clincal Site #129 Ramat Gan Israel 5265601
    114 Exelixis Clinical Site #41 Meldola Forli - Cesena Italy 47014
    115 Exelixis Clinical Site #70 Faenza Ravenna Italy 48018
    116 Exelixis Clinical Site #170 Candiolo Torino Italy 10060
    117 Exelixis Clinical Site #47 Arezzo Italy 52100
    118 Exelixis Clinical Site #60 Modena Italy 41124
    119 Exelixis Clinical Site #61 Padova Italy 35128
    120 Exelixis Clinical Site #59 Pavia Italy 27100
    121 Exelixis Clinical Site #104 Perugia Italy 06132
    122 Exelixis Clinical Site #68 Terni Italy 05100
    123 Exelixis Clinical Site #147 Seongnam-si Gyeonggi-do Korea, Republic of 13620
    124 Exelixis Clinical Site #145 Yangsan Gyeongsangnam-do Korea, Republic of 50612
    125 Exelixis Clinical Site #143 Seoul Korea, Republic of 03722
    126 Exelixis Clinical Site #151 Seoul Korea, Republic of 05505
    127 Exelixis Clinical Site #152 Seoul Korea, Republic of 06351
    128 Exelixis Clinical Site #123 Aguascalientes Ags Mexico 20116
    129 Exelixis Clinical Site #167 León Guanajuato Mexico 37000
    130 Exelixis Clinical Site #169 Zapopan Jalisco Mexico 45070
    131 Exelixis Clinical Site #134 Monterrey Nuevo León Mexico 64710
    132 Exelixis Clinical Site #132 Oaxaca de Juarez Oaxaca Mexico 68000
    133 Exelixis Clinical Site #160 Ciudad de México Mexico 03100
    134 Exelixis Clinical Site #131 Querétaro Mexico 76000
    135 Exelixis Clinical Site #161 Querétaro Mexico 76090
    136 Exelixis Clinical Site #144 Amsterdam Netherlands 1105 AZ
    137 Exelixis Clinical Site #149 Rotterdam Netherlands 3015 GD
    138 Exelixis Clinical Site #122 Hamilton Waikato New Zealand 3204
    139 Exelixis Clinical Site #148 Newtown Wellington New Zealand 6021
    140 Exelixis Clinical Site #31 Biała Podlaska Poland 21-500
    141 Exelixis Clinical Site #62 Bydgoszcz Poland 85-796
    142 Exelixis Clinical Site #135 Gdańsk Poland 80-219
    143 Exelixis Clinical Site #99 Otwock Poland 05-400
    144 Exelixis Clinical Site #83 Poznań Poland 60-693
    145 Exelixis Clinical Site #77 Singapore Singapore 119074
    146 Exelixis Clinical Site #40 Singapore Singapore 169610
    147 Exelixis Clinical Site #53 Santiago De Compostela Coruña Spain 15706
    148 Exelixis Clinical Site #45 Pamplona Navarra Spain 31008
    149 Exelixis Clinical Site #43 Barcelona Spain 08035
    150 Exelixis Clinical Site #36 Barcelona Spain 08036
    151 Exelixis Clinical Site #49 Córdoba Spain 14004
    152 Exelixis Clinical Site #34 Madrid Spain 28009
    153 Exelixis Clinical Site #94 Madrid Spain 28040
    154 Exelixis Clinical Site #20 Madrid Spain 28041
    155 Exelixis Clinical Site #55 Madrid Spain 28050
    156 Exelixis Clinical Site #96 Oviedo Spain 33011
    157 Exelixis Clinical Site #74 Valencia Spain 46009
    158 Exelixis Clinical Site #174 Kaohsiung City Taiwan 83301
    159 Exelixis Clinical Site #142 Taichung Taiwan 404
    160 Exelixis Clinical Site #138 Taipei Taiwan 10002
    161 Exelixis Clinical Site #173 Taoyuan Taiwan 333
    162 Exelixis Clinical Site #72 Cambridge United Kingdom CB2 0QQ
    163 Exelixis Clinical Site #93 Glasgow United Kingdom G12 0YN
    164 Exelixis Clinical Site #30 London United Kingdom EC1A 7BE
    165 Exelixis Clinical Site #106 London United Kingdom SE1 9RT
    166 Exelixis Clinical Site #172 London United Kingdom W6 8RF
    167 Exelixis Clinical Site #92 Manchester United Kingdom M20 4BX

    Sponsors and Collaborators

    • Exelixis

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Exelixis
    ClinicalTrials.gov Identifier:
    NCT03937219
    Other Study ID Numbers:
    • XL184-313
    First Posted:
    May 3, 2019
    Last Update Posted:
    Mar 10, 2022
    Last Verified:
    Mar 1, 2022
    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:
    Carcinoma
    Carcinoma, Renal Cell
    Nivolumab
    Ipilimumab

    Study Results

    No Results Posted as of Mar 10, 2022