Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03937219




Registration number
NCT03937219
Ethics application status
Date submitted
2/05/2019
Date registered
3/05/2019
Date last updated
12/11/2024

Titles & IDs
Public title
Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
Scientific 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
Secondary ID [1] 0 0
XL184-313
Universal Trial Number (UTN)
Trial acronym
COSMIC-313
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabozantinib
Treatment: Other - Nivolumab
Treatment: Other - Ipilimumab
Treatment: Drugs - Cabozantinib-matched placebo

Experimental: Experimental Arm - Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab

Active comparator: Control Arm - Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab


Treatment: Drugs: Cabozantinib
Specified dose on specified days.

Treatment: Other: Nivolumab
Specified dose on specified days.

Treatment: Other: Ipilimumab
Specified dose on specified days.

Treatment: Drugs: Cabozantinib-matched placebo
Specified dose on specified days.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Duration of Progression-Free Survival (PFS) per RECIST 1.1 as determined by blinded independent radiology committee (BIRC)
Timepoint [1] 0 0
Up to 23 months after first subject randomized
Secondary outcome [1] 0 0
Duration of Overall Survival (OS)
Timepoint [1] 0 0
Up to 69 months after first subject randomized

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/05/2024
Sample size
Target
Accrual to date
Final
855
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Exelixis Clinical Site #32 - Albury
Recruitment hospital [2] 0 0
Exelixis Clinical Site #35 - Kogarah
Recruitment hospital [3] 0 0
Exelixis Clinical Site #27 - North Ryde
Recruitment hospital [4] 0 0
Exelixis Clinical Site #33 - Sydney
Recruitment hospital [5] 0 0
Exelixis Clinical Site #17 - South Brisbane
Recruitment hospital [6] 0 0
Exelixis Clinical Site #14 - Woolloongabba
Recruitment hospital [7] 0 0
Exelixis Clinical Site #18 - Adelaide
Recruitment hospital [8] 0 0
Exelixis Clinical Site #11 - North Adelaide
Recruitment hospital [9] 0 0
Exelixis Clinical Site #9 - Ballarat
Recruitment hospital [10] 0 0
Exelixis Clinical Site #23 - Box Hill
Recruitment hospital [11] 0 0
Exelixis Clinical Site #26 - Subiaco
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2109 - North Ryde
Recruitment postcode(s) [4] 0 0
2065 - Sydney
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
5006 - North Adelaide
Recruitment postcode(s) [9] 0 0
3350 - Ballarat
Recruitment postcode(s) [10] 0 0
3128 - Box Hill
Recruitment postcode(s) [11] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maine
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
United States of America
State/province [19] 0 0
Wisconsin
Country [20] 0 0
Argentina
State/province [20] 0 0
Provincia De Buenos Aires
Country [21] 0 0
Argentina
State/province [21] 0 0
Santa Fe
Country [22] 0 0
Argentina
State/province [22] 0 0
Tucumán
Country [23] 0 0
Argentina
State/province [23] 0 0
Caba
Country [24] 0 0
Argentina
State/province [24] 0 0
Ciudad Autonoma de Buenos Aires
Country [25] 0 0
Argentina
State/province [25] 0 0
Ciudad Autonoma de Buenos Aire
Country [26] 0 0
Argentina
State/province [26] 0 0
Córdoba
Country [27] 0 0
Austria
State/province [27] 0 0
Niederösterreich
Country [28] 0 0
Austria
State/province [28] 0 0
Oberösterreich
Country [29] 0 0
Austria
State/province [29] 0 0
Salzburg
Country [30] 0 0
Austria
State/province [30] 0 0
Vienna
Country [31] 0 0
Belgium
State/province [31] 0 0
Brussels
Country [32] 0 0
Belgium
State/province [32] 0 0
Hasselt
Country [33] 0 0
Brazil
State/province [33] 0 0
Minas Gerais
Country [34] 0 0
Brazil
State/province [34] 0 0
Parana
Country [35] 0 0
Brazil
State/province [35] 0 0
Rio Grande Do Sul
Country [36] 0 0
Brazil
State/province [36] 0 0
RS
Country [37] 0 0
Brazil
State/province [37] 0 0
São Paulo
Country [38] 0 0
Canada
State/province [38] 0 0
Alberta
Country [39] 0 0
Canada
State/province [39] 0 0
Manitoba
Country [40] 0 0
Canada
State/province [40] 0 0
Ontario
Country [41] 0 0
Canada
State/province [41] 0 0
Quebec
Country [42] 0 0
Chile
State/province [42] 0 0
Región De La Araucanía (IX)
Country [43] 0 0
Chile
State/province [43] 0 0
Santiago
Country [44] 0 0
Czechia
State/province [44] 0 0
Králová
Country [45] 0 0
Czechia
State/province [45] 0 0
Praha 4
Country [46] 0 0
Czechia
State/province [46] 0 0
Praha 5
Country [47] 0 0
Finland
State/province [47] 0 0
Helsinki
Country [48] 0 0
Finland
State/province [48] 0 0
Tampere
Country [49] 0 0
Finland
State/province [49] 0 0
Turku
Country [50] 0 0
France
State/province [50] 0 0
Bordeaux
Country [51] 0 0
France
State/province [51] 0 0
Le Mans
Country [52] 0 0
France
State/province [52] 0 0
Lyon Cedex 8
Country [53] 0 0
France
State/province [53] 0 0
Montpellier Cedex 5
Country [54] 0 0
France
State/province [54] 0 0
Nice Cedex 2
Country [55] 0 0
France
State/province [55] 0 0
Paris
Country [56] 0 0
France
State/province [56] 0 0
Reims Cedex
Country [57] 0 0
France
State/province [57] 0 0
Rennes
Country [58] 0 0
France
State/province [58] 0 0
Strasbourg
Country [59] 0 0
France
State/province [59] 0 0
Toulouse Cedex 9
Country [60] 0 0
France
State/province [60] 0 0
Vandœuvre-lès-Nancy
Country [61] 0 0
France
State/province [61] 0 0
Villejuif
Country [62] 0 0
Germany
State/province [62] 0 0
Baden-Württemberg
Country [63] 0 0
Germany
State/province [63] 0 0
Hessen
Country [64] 0 0
Germany
State/province [64] 0 0
Nordrhein-Westfalen
Country [65] 0 0
Germany
State/province [65] 0 0
Rheinland-Pfalz
Country [66] 0 0
Germany
State/province [66] 0 0
Thüringen
Country [67] 0 0
Germany
State/province [67] 0 0
Dresden
Country [68] 0 0
Hong Kong
State/province [68] 0 0
Hong Kong
Country [69] 0 0
Hong Kong
State/province [69] 0 0
Shatin
Country [70] 0 0
Hong Kong
State/province [70] 0 0
Tuen Mun
Country [71] 0 0
Hungary
State/province [71] 0 0
Budapest
Country [72] 0 0
Hungary
State/province [72] 0 0
Pécs
Country [73] 0 0
Israel
State/province [73] 0 0
Be'er Sheva
Country [74] 0 0
Israel
State/province [74] 0 0
Haifa
Country [75] 0 0
Israel
State/province [75] 0 0
Jerusalem
Country [76] 0 0
Israel
State/province [76] 0 0
Kfar Saba
Country [77] 0 0
Israel
State/province [77] 0 0
Petach Tikva
Country [78] 0 0
Israel
State/province [78] 0 0
Ramat Gan
Country [79] 0 0
Italy
State/province [79] 0 0
Forli - Cesena
Country [80] 0 0
Italy
State/province [80] 0 0
Ravenna
Country [81] 0 0
Italy
State/province [81] 0 0
Arezzo
Country [82] 0 0
Italy
State/province [82] 0 0
Modena
Country [83] 0 0
Italy
State/province [83] 0 0
Padova
Country [84] 0 0
Italy
State/province [84] 0 0
Pavia
Country [85] 0 0
Italy
State/province [85] 0 0
Perugia
Country [86] 0 0
Italy
State/province [86] 0 0
Terni
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Gyeonggi-do
Country [88] 0 0
Korea, Republic of
State/province [88] 0 0
Seoul
Country [89] 0 0
Mexico
State/province [89] 0 0
Ags
Country [90] 0 0
Mexico
State/province [90] 0 0
Guanajuato
Country [91] 0 0
Mexico
State/province [91] 0 0
Jalisco
Country [92] 0 0
Mexico
State/province [92] 0 0
Nuevo León
Country [93] 0 0
Mexico
State/province [93] 0 0
Oaxaca
Country [94] 0 0
Mexico
State/province [94] 0 0
Ciudad de México
Country [95] 0 0
Mexico
State/province [95] 0 0
Querétaro
Country [96] 0 0
Netherlands
State/province [96] 0 0
Amsterdam
Country [97] 0 0
Netherlands
State/province [97] 0 0
Rotterdam
Country [98] 0 0
New Zealand
State/province [98] 0 0
Waikato
Country [99] 0 0
New Zealand
State/province [99] 0 0
Wellington
Country [100] 0 0
Poland
State/province [100] 0 0
Biala Podlaska
Country [101] 0 0
Poland
State/province [101] 0 0
Bydgoszcz
Country [102] 0 0
Poland
State/province [102] 0 0
Gdansk
Country [103] 0 0
Poland
State/province [103] 0 0
Otwock
Country [104] 0 0
Poland
State/province [104] 0 0
Poznan
Country [105] 0 0
Singapore
State/province [105] 0 0
Singapore
Country [106] 0 0
Spain
State/province [106] 0 0
Coruña
Country [107] 0 0
Spain
State/province [107] 0 0
Navarra
Country [108] 0 0
Spain
State/province [108] 0 0
Barcelona
Country [109] 0 0
Spain
State/province [109] 0 0
Córdoba
Country [110] 0 0
Spain
State/province [110] 0 0
Madrid
Country [111] 0 0
Spain
State/province [111] 0 0
Oviedo
Country [112] 0 0
Spain
State/province [112] 0 0
Valencia
Country [113] 0 0
Taiwan
State/province [113] 0 0
Taichung
Country [114] 0 0
Taiwan
State/province [114] 0 0
Taipei
Country [115] 0 0
Taiwan
State/province [115] 0 0
Taoyuan
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Cambridge
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Glasgow
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Exelixis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03937219
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03937219