Clinical trial NCT03937219: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Renal Cell Carcinoma
Keywords: renal
cancer
carcinoma
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2019-05-03
Enrollment: 855
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).

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. Measurable disease must be outside the radiation field if radiation therapy was previously administered.
* 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.
* 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.

Primary outcomes:
measure: Duration of Progression-Free Survival (PFS) per RECIST 1.1 as determined by blinded independent radiology committee (BIRC)
timeFrame: Up to 23 months after first subject randomized
Secondary outcomes:
measure: Duration of Overall Survival (OS)
timeFrame: Up to 69 months after first subject randomized
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Exelixis Clinical Site #116
state: California
city: Orange
country: United States
facility: Exelixis Clinical Site #166
state: California
city: Boca Raton
country: United States
facility: Exelixis Clinical Site #29
state: Florida
city: Miami
country: United States
facility: Exelixis Clinical Site #44
state: Florida
city: Atlanta
country: United States
facility: Exelixis Clinical Site #3
state: Georgia
city: Chicago
country: United States
facility: Exelixis Clinical Site #95
state: Illinois
city: Scarborough
country: United States
facility: Exelixis Clinical Site #69
state: Maine
city: Baltimore
country: United States
facility: Exelixis Clinical Site #58A
state: Maryland
city: Boston
country: United States
facility: Exelixis Clinical Site #7B
state: Massachusetts
city: Boston
country: United States
facility: Exelixis Clinical Site #7A
state: Massachusetts
city: Boston
country: United States
facility: Exelixis Clinical Site #7C
state: Massachusetts
city: Burlington
country: United States
facility: Exelixis Clinical Site #6
state: Massachusetts
city: Detroit
country: United States
facility: Exelixis Clinical Site #15
state: Michigan
city: Kansas City
country: United States
facility: Exelixis Clinical Site #24
state: Missouri
city: Saint Louis
country: United States
facility: Exelixis Clinical Site #4
state: Missouri
city: Omaha
country: United States
facility: Exelixis Clinical Site #2
state: Nebraska
city: New York
country: United States
facility: Exelixis Clinical Site #159
state: New York
city: New York
country: United States
facility: Exelixis Clinical Site #8
state: New York
city: Syracuse
country: United States
facility: Exelixis Clinical Site #19
state: New York
city: Charlotte
country: United States
facility: Exelixis Clinical Site #101
state: North Carolina
city: Portland
country: United States
facility: Exelixis Clinical Site #107
state: Oregon
city: Pittsburgh
country: United States
facility: Exelixis Clinical Site #12
state: Pennsylvania
city: Charleston
country: United States
facility: Exelixis Clinical Site #102
state: South Carolina
city: Myrtle Beach
country: United States
facility: Exelixis Clinical Site #5
state: South Carolina
city: Nashville
country: United States
facility: Exelixis Clinical Site #10
state: Tennessee
city: Nashville
country: United States
facility: Exelixis Clinical Site #38
state: Tennessee
city: Fairfax
country: United States
facility: Exelixis Clinical Site #64
state: Virginia
city: Seattle
country: United States
facility: Exelixis Clinical Site #57
state: Washington
city: Spokane
country: United States
facility: Exelixis Clinical Site #1
state: Washington
city: Madison
country: United States
facility: Exelixis Clinical Site #13
state: Wisconsin
city: Pilar
country: Argentina
facility: Exelixis Clinical Site #153
state: Provincia De Buenos Aires
city: Rosario
country: Argentina
facility: Exelixis Clinical Site #109
state: Santa Fe
city: San Miguel De Tucumán
country: Argentina
facility: Exelixis Clinical Site #73
state: Tucumán
city: Caba
country: Argentina
facility: Exelixis Clinical Site #63
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Exelixis Clinical Site #54
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Exelixis Clinical Site #110
city: Córdoba
country: Argentina
facility: Exelixis Clinical Site #120
city: Albury
country: Australia
facility: Exelixis Clinical Site #32
state: New South Wales
city: Kogarah
country: Australia
facility: Exelixis Clinical Site #35
state: New South Wales
city: North Ryde
country: Australia
facility: Exelixis Clinical Site #27
state: New South Wales
city: Sydney
country: Australia
facility: Exelixis Clinical Site #33
state: New South Wales
city: South Brisbane
country: Australia
facility: Exelixis Clinical Site #17
state: Queensland
city: Woolloongabba
country: Australia
facility: Exelixis Clinical Site #14
state: Queensland
city: Adelaide
country: Australia
facility: Exelixis Clinical Site #18
state: South Australia
city: North Adelaide
country: Australia
facility: Exelixis Clinical Site #11
state: South Australia
city: Ballarat
country: Australia
facility: Exelixis Clinical Site #9
state: Victoria
city: Box Hill
country: Australia
facility: Exelixis Clinical Site #23
state: Victoria
city: Subiaco
country: Australia
facility: Exelixis Clinical Site #26
state: Western Australia
city: Wiener Neustadt
country: Austria
facility: Exelixis Clinical Site #98
state: Niederösterreich
city: Linz
country: Austria
facility: Exelixis Clinical Site #76
state: Oberösterreich
city: Salzburg
country: Austria
facility: Exelixis Clinical Site #75
city: Vienna
country: Austria
facility: Exelixis Clinical Site #126
city: Brussels
country: Belgium
facility: Exelixis Clinical Site #112
city: Hasselt
country: Belgium
facility: Exelixis Clinical Site #146
city: Belo Horizonte
country: Brazil
facility: Exelixis Clinical Site #154
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Exelixis Clinical Site #155
state: Parana
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #140
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #163
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #158
state: RS
city: Barretos
country: Brazil
facility: Exelixis Clinical Site #168
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Exelixis Clinical Site #162
state: São Paulo
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #119
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #141
city: Calgary
country: Canada
facility: Exelixis Clinical Site #22
state: Alberta
city: Winnipeg
country: Canada
facility: Exelixis Clinical Site #105
state: Manitoba
city: Ottawa
country: Canada
facility: Exelixis Clinical Site #46
state: Ontario
city: Toronto
country: Canada
facility: Exelixis Clinical Site #25
state: Ontario
city: Montréal
country: Canada
facility: Exelixis Clinical Site #113
state: Quebec
city: Temuco
country: Chile
facility: Exelixis Clinical Site #85
state: Región De La Araucanía (IX)
city: Santiago
country: Chile
facility: Exelixis Clinical Site #91
city: Santiago
country: Chile
facility: Exelixis Clinical Site #100
city: Králová
country: Czechia
facility: Exelixis Clinical Site #89
city: Praha 4
country: Czechia
facility: Exelixis Clinical Site #114
city: Praha 5
country: Czechia
facility: Exelixis Clinical Site #118
city: Helsinki
country: Finland
facility: Exelixis Clinical Site #50
city: Tampere
country: Finland
facility: Exelixis Clinical Site #56
city: Turku
country: Finland
facility: Exelixis Clinical Site #52
city: Bordeaux
country: France
facility: Exelixis Clinical Site #86
city: Le Mans
country: France
facility: Exelixis Clinical Site #71
city: Lyon Cedex 8
country: France
facility: Exelixis Clinical Site #78
city: Montpellier Cedex 5
country: France
facility: Exelixis Clinical Site #80
city: Nice Cedex 2
country: France
facility: Exelixis Clinical Site #66
city: Paris
country: France
facility: Exelixis Clinical Site #150
city: Reims Cedex
country: France
facility: Exelixis Clinical Site #65
city: Rennes
country: France
facility: Exelixis Clinical Site #125
city: Strasbourg
country: France
facility: Exelixis Clinical Site #128
city: Strasbourg
country: France
facility: Exelixis Clinical Site #90
city: Toulouse Cedex 9
country: France
facility: Exelixis Clinical Site #42
city: Vandœuvre-lès-Nancy
country: France
facility: Exelixis Clinical Site #67
city: Villejuif
country: France
facility: Exelixis Clinical Site #37
city: Heidelberg
country: Germany
facility: Exelixis Clinical Site #127
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Exelixis Clinical Site #115
state: Baden-Württemberg
city: Frankfurt am main
country: Germany
facility: Exelixis Clinical Site #117
state: Hessen
city: Münster
country: Germany
facility: Exelixis Clinical Site #139
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Exelixis Clinical Site #171
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Exelixis Clinical Site #164
state: Rheinland-Pfalz
city: Jena
country: Germany
facility: Exelixis Clinical Site #137
state: Thüringen
city: Dresden
country: Germany
facility: Exelixis Clinical Site #124
city: Hong Kong
country: Hong Kong
facility: Exelixis Clinical Site #28
city: Shatin
country: Hong Kong
facility: Exelixis Clinical Site #136
city: Tuen Mun
country: Hong Kong
facility: Exelixis Clinical Site #111
city: Budapest
country: Hungary
facility: Exelixis Clinical Site #39
city: Pécs
country: Hungary
facility: Exelixis Clinical Site #51
city: Be'er Sheva
country: Israel
facility: Exelixis Clinical Site #88
city: Haifa
country: Israel
facility: Exelixis Clinical Site #81
city: Jerusalem
country: Israel
facility: Exelixis Clinical Site #84
city: Kfar Saba
country: Israel
facility: Exelixis Clinical Site #121
city: Petach Tikva
country: Israel
facility: Exelixis Clinical Site #97
city: Ramat Gan
country: Israel
facility: Exelixis Clincal Site #129
city: Meldola
country: Italy
facility: Exelixis Clinical Site #41
state: Forli - Cesena
city: Faenza
country: Italy
facility: Exelixis Clinical Site #70
state: Ravenna
city: Arezzo
country: Italy
facility: Exelixis Clinical Site #47
city: Modena
country: Italy
facility: Exelixis Clinical Site #60
city: Padova
country: Italy
facility: Exelixis Clinical Site #61
city: Pavia
country: Italy
facility: Exelixis Clinical Site #59
city: Perugia
country: Italy
facility: Exelixis Clinical Site #104
city: Terni
country: Italy
facility: Exelixis Clinical Site #68
city: Seongnam-si
country: Korea, Republic of
facility: Exelixis Clinical Site #147
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #143
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #151
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #152
city: Aguascalientes
country: Mexico
facility: Exelixis Clinical Site #123
state: Ags
city: León
country: Mexico
facility: Exelixis Clinical Site #167
state: Guanajuato
city: Zapopan
country: Mexico
facility: Exelixis Clinical Site #169
state: Jalisco
city: Monterrey
country: Mexico
facility: Exelixis Clinical Site #134
state: Nuevo León
city: Oaxaca de Juarez
country: Mexico
facility: Exelixis Clinical Site #132
state: Oaxaca
city: Ciudad de México
country: Mexico
facility: Exelixis Clinical Site #160
city: Querétaro
country: Mexico
facility: Exelixis Clinical Site #131
city: Querétaro
country: Mexico
facility: Exelixis Clinical Site #161
city: Amsterdam
country: Netherlands
facility: Exelixis Clinical Site #144
city: Rotterdam
country: Netherlands
facility: Exelixis Clinical Site #149
city: Hamilton
country: New Zealand
facility: Exelixis Clinical Site #122
state: Waikato
city: Newtown
country: New Zealand
facility: Exelixis Clinical Site #148
state: Wellington
city: Biała Podlaska
country: Poland
facility: Exelixis Clinical Site #31
city: Bydgoszcz
country: Poland
facility: Exelixis Clinical Site #62
city: Gdańsk
country: Poland
facility: Exelixis Clinical Site #135
city: Otwock
country: Poland
facility: Exelixis Clinical Site #99
city: Poznań
country: Poland
facility: Exelixis Clinical Site #83
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #77
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #40
city: Santiago De Compostela
country: Spain
facility: Exelixis Clinical Site #53
state: Coruña
city: Pamplona
country: Spain
facility: Exelixis Clinical Site #45
state: Navarra
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #43
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #36
city: Córdoba
country: Spain
facility: Exelixis Clinical Site #49
city: Madrid
country: Spain
facility: Exelixis Clinical Site #34
city: Madrid
country: Spain
facility: Exelixis Clinical Site #94
city: Madrid
country: Spain
facility: Exelixis Clinical Site #20
city: Madrid
country: Spain
facility: Exelixis Clinical Site #55
city: Oviedo
country: Spain
facility: Exelixis Clinical Site #96
city: Valencia
country: Spain
facility: Exelixis Clinical Site #74
city: Taichung
country: Taiwan
facility: Exelixis Clinical Site #142
city: Taipei
country: Taiwan
facility: Exelixis Clinical Site #138
city: Taoyuan
country: Taiwan
facility: Exelixis Clinical Site #173
city: Cambridge
country: United Kingdom
facility: Exelixis Clinical Site #72
city: Glasgow
country: United Kingdom
facility: Exelixis Clinical Site #93
city: London
country: United Kingdom
facility: Exelixis Clinical Site #30
city: London
country: United Kingdom
facility: Exelixis Clinical Site #172
city: Manchester
country: United Kingdom
facility: Exelixis Clinical Site #92
Study officials:
References:
citation: Labriola MK, George DJ. Setting a new standard for long-term survival in metastatic kidney cancer. Cancer. 2022 Jun 1;128(11):2058-2060. doi: 10.1002/cncr.34177. Epub 2022 Apr 5. No abstract available.
citation: Mar N, Kaakour D, Rezazadeh Kalebasty A. Renal Cell Carcinoma-Lessons in Diversity, Breakthroughs, and Challenges. JCO Oncol Pract. 2022 Mar;18(3):197-199. doi: 10.1200/OP.21.00446. Epub 2021 Sep 22. No abstract available.
citation: Hofmann F, Hwang EC, Lam TB, Bex A, Yuan Y, Marconi LS, Ljungberg B. Targeted therapy for metastatic renal cell carcinoma. Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD012796. doi: 10.1002/14651858.CD012796.pub2.