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

Renal Cell Carcinoma Clinical Trial

— COSMIC-313  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03937219
• Other study ID #: XL184-313
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 25, 2019
• Est. completion date: March 2025

Study information

• Verified date: April 2023
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 840
• Est. completion date: March 2025
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Cabozantinib
Specified dose on specified days.

Biological:
• Nivolumab
Specified dose on specified days.
• Ipilimumab
Specified dose on specified days.

Drug:
• Cabozantinib-matched placebo
Specified dose on specified days.

Locations

Country	Name	City	State
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 #153	Pilar	Provincia De Buenos Aires
Argentina	Exelixis Clinical Site #109	Rosario	Santa Fe
Argentina	Exelixis Clinical Site #73	San Miguel De Tucumán	Tucumán
Australia	Exelixis Clinical Site #18	Adelaide	South Australia
Australia	Exelixis Clinical Site #32	Albury	New South Wales
Australia	Exelixis Clinical Site #9	Ballarat	Victoria
Australia	Exelixis Clinical Site #23	Box Hill	Victoria
Australia	Exelixis Clinical Site #35	Kogarah	New South Wales
Australia	Exelixis Clinical Site #11	North Adelaide	South Australia
Australia	Exelixis Clinical Site #27	North Ryde	New South Wales
Australia	Exelixis Clinical Site #17	South Brisbane	Queensland
Australia	Exelixis Clinical Site #26	Subiaco	Western Australia
Australia	Exelixis Clinical Site #33	Sydney	New South Wales
Australia	Exelixis Clinical Site #14	Woolloongabba	Queensland
Austria	Exelixis Clinical Site #76	Linz	Oberösterreich
Austria	Exelixis Clinical Site #75	Salzburg
Austria	Exelixis Clinical Site #126	Vienna
Austria	Exelixis Clinical Site #98	Wiener Neustadt	Niederösterreich
Belgium	Exelixis Clinical Site #112	Brussels
Belgium	Exelixis Clinical Site #146	Hasselt
Brazil	Exelixis Clinical Site #168	Barretos	São Paulo
Brazil	Exelixis Clinical Site #154	Belo Horizonte	Minas Gerais
Brazil	Exelixis Clinical Site #155	Curitiba	Parana
Brazil	Exelixis Clinical Site #140	Porto Alegre	Rio Grande Do Sul
Brazil	Exelixis Clinical Site #158	Porto Alegre	RS
Brazil	Exelixis Clinical Site #163	Porto Alegre	Rio Grande Do Sul
Brazil	Exelixis Clinical Site #162	São José Do Rio Preto	São Paulo
Brazil	Exelixis Clinical Site #119	São Paulo
Brazil	Exelixis Clinical Site #141	São Paulo
Canada	Exelixis Clinical Site #22	Calgary	Alberta
Canada	Exelixis Clinical Site #113	Montréal	Quebec
Canada	Exelixis Clinical Site #46	Ottawa	Ontario
Canada	Exelixis Clinical Site #25	Toronto	Ontario
Canada	Exelixis Clinical Site #105	Winnipeg	Manitoba
Chile	Exelixis Clinical Site #100	Santiago
Chile	Exelixis Clinical Site #91	Santiago
Chile	Exelixis Clinical Site #85	Temuco	Región De La Araucanía (IX)
Czechia	Exelixis Clinical Site #89	Králová
Czechia	Exelixis Clinical Site #114	Praha 4
Czechia	Exelixis Clinical Site #118	Praha 5
Finland	Exelixis Clinical Site #50	Helsinki
Finland	Exelixis Clinical Site #56	Tampere
Finland	Exelixis Clinical Site #52	Turku
France	Exelixis Clinical Site #86	Bordeaux
France	Exelixis Clinical Site #71	Le Mans
France	Exelixis Clinical Site #78	Lyon Cedex 8
France	Exelixis Clinical Site #80	Montpellier Cedex 5
France	Exelixis Clinical Site #66	Nice Cedex 2
France	Exelixis Clinical Site #150	Paris
France	Exelixis Clinical Site #65	Reims Cedex
France	Exelixis Clinical Site #125	Rennes
France	Exelixis Clinical Site #128	Strasbourg
France	Exelixis Clinical Site #90	Strasbourg
France	Exelixis Clinical Site #42	Toulouse Cedex 9
France	Exelixis Clinical Site #67	Vandœuvre-lès-Nancy
France	Exelixis Clinical Site #37	Villejuif
Germany	Exelixis Clinical Site #124	Dresden
Germany	Exelixis Clinical Site #117	Frankfurt am main	Hessen
Germany	Exelixis Clinical Site #127	Heidelberg	Baden-Württemberg
Germany	Exelixis Clinical Site #137	Jena	Thüringen
Germany	Exelixis Clinical Site #164	Mainz	Rheinland-Pfalz
Germany	Exelixis Clinical Site #139	Münster	Nordrhein-Westfalen
Germany	Exelixis Clinical Site #171	Münster	Nordrhein-Westfalen
Germany	Exelixis Clinical Site #115	Tübingen	Baden-Württemberg
Hong Kong	Exelixis Clinical Site #28	Hong Kong
Hong Kong	Exelixis Clinical Site #136	Shatin
Hong Kong	Exelixis Clinical Site #111	Tuen Mun
Hungary	Exelixis Clinical Site #39	Budapest
Hungary	Exelixis Clinical Site #51	Pécs
Israel	Exelixis Clinical Site #88	Be'er Sheva
Israel	Exelixis Clinical Site #81	Haifa
Israel	Exelixis Clinical Site #84	Jerusalem
Israel	Exelixis Clinical Site #121	Kfar Saba
Israel	Exelixis Clinical Site #97	Petach Tikva
Israel	Exelixis Clincal Site #129	Ramat Gan
Italy	Exelixis Clinical Site #47	Arezzo
Italy	Exelixis Clinical Site #70	Faenza	Ravenna
Italy	Exelixis Clinical Site #41	Meldola	Forli - Cesena
Italy	Exelixis Clinical Site #60	Modena
Italy	Exelixis Clinical Site #61	Padova
Italy	Exelixis Clinical Site #59	Pavia
Italy	Exelixis Clinical Site #104	Perugia
Italy	Exelixis Clinical Site #68	Terni
Korea, Republic of	Exelixis Clinical Site #147	Seongnam-si	Gyeonggi-do
Korea, Republic of	Exelixis Clinical Site #143	Seoul
Korea, Republic of	Exelixis Clinical Site #151	Seoul
Korea, Republic of	Exelixis Clinical Site #152	Seoul
Mexico	Exelixis Clinical Site #123	Aguascalientes	Ags
Mexico	Exelixis Clinical Site #160	Ciudad de México
Mexico	Exelixis Clinical Site #167	León	Guanajuato
Mexico	Exelixis Clinical Site #134	Monterrey	Nuevo León
Mexico	Exelixis Clinical Site #132	Oaxaca de Juarez	Oaxaca
Mexico	Exelixis Clinical Site #131	Querétaro
Mexico	Exelixis Clinical Site #161	Querétaro
Mexico	Exelixis Clinical Site #169	Zapopan	Jalisco
Netherlands	Exelixis Clinical Site #144	Amsterdam
Netherlands	Exelixis Clinical Site #149	Rotterdam
New Zealand	Exelixis Clinical Site #122	Hamilton	Waikato
New Zealand	Exelixis Clinical Site #148	Newtown	Wellington
Poland	Exelixis Clinical Site #31	Biala Podlaska
Poland	Exelixis Clinical Site #62	Bydgoszcz
Poland	Exelixis Clinical Site #135	Gdansk
Poland	Exelixis Clinical Site #99	Otwock
Poland	Exelixis Clinical Site #83	Poznan
Singapore	Exelixis Clinical Site #40	Singapore
Singapore	Exelixis Clinical Site #77	Singapore
Spain	Exelixis Clinical Site #36	Barcelona
Spain	Exelixis Clinical Site #43	Barcelona
Spain	Exelixis Clinical Site #49	Córdoba
Spain	Exelixis Clinical Site #20	Madrid
Spain	Exelixis Clinical Site #34	Madrid
Spain	Exelixis Clinical Site #55	Madrid
Spain	Exelixis Clinical Site #94	Madrid
Spain	Exelixis Clinical Site #96	Oviedo
Spain	Exelixis Clinical Site #45	Pamplona	Navarra
Spain	Exelixis Clinical Site #53	Santiago De Compostela	Coruña
Spain	Exelixis Clinical Site #74	Valencia
Taiwan	Exelixis Clinical Site #142	Taichung
Taiwan	Exelixis Clinical Site #138	Taipei
Taiwan	Exelixis Clinical Site #173	Taoyuan
United Kingdom	Exelixis Clinical Site #72	Cambridge
United Kingdom	Exelixis Clinical Site #93	Glasgow
United Kingdom	Exelixis Clinical Site #172	London
United Kingdom	Exelixis Clinical Site #30	London
United Kingdom	Exelixis Clinical Site #92	Manchester
United States	Exelixis Clinical Site #3	Atlanta	Georgia
United States	Exelixis Clinical Site #58A	Baltimore	Maryland
United States	Exelixis Clinical Site #29	Boca Raton	Florida
United States	Exelixis Clinical Site #7A	Boston	Massachusetts
United States	Exelixis Clinical Site #7B	Boston	Massachusetts
United States	Exelixis Clinical Site #7C	Boston	Massachusetts
United States	Exelixis Clinical Site #6	Burlington	Massachusetts
United States	Exelixis Clinical Site #102	Charleston	South Carolina
United States	Exelixis Clinical Site #101	Charlotte	North Carolina
United States	Exelixis Clinical Site #95	Chicago	Illinois
United States	Exelixis Clinical Site #15	Detroit	Michigan
United States	Exelixis Clinical Site #64	Fairfax	Virginia
United States	Exelixis Clinical Site #24	Kansas City	Missouri
United States	Exelixis Clinical Site #116	La Jolla	California
United States	Exelixis Clinical Site #13	Madison	Wisconsin
United States	Exelixis Clinical Site #44	Miami	Florida
United States	Exelixis Clinical Site #5	Myrtle Beach	South Carolina
United States	Exelixis Clinical Site #10	Nashville	Tennessee
United States	Exelixis Clinical Site #38	Nashville	Tennessee
United States	Exelixis Clinical Site #159	New York	New York
United States	Exelixis Clinical Site #8	New York	New York
United States	Exelixis Clinical Site #2	Omaha	Nebraska
United States	Exelixis Clinical Site #166	Orange	California
United States	Exelixis Clinical Site #12	Pittsburgh	Pennsylvania
United States	Exelixis Clinical Site #107	Portland	Oregon
United States	Exelixis Clinical Site #4	Saint Louis	Missouri
United States	Exelixis Clinical Site #69	Scarborough	Maine
United States	Exelixis Clinical Site #57	Seattle	Washington
United States	Exelixis Clinical Site #1	Spokane	Washington
United States	Exelixis Clinical Site #19	Syracuse	New York
United States	Exelixis Clinical Site #58B	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  Finland,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Duration of Overall Survival (OS)		Up to 69 months after first subject randomized