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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03937219




Registration number
NCT03937219
Ethics application status
Date submitted
2/05/2019
Date registered
3/05/2019
Date last updated
13/04/2023

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
Other interventions - Nivolumab
Other interventions - 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.

Other interventions: Nivolumab
Specified dose on specified days.

Other interventions: 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
Other interventions
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
Active, not recruiting
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
1/03/2025
Actual
Sample size
Target
840
Accrual to date
Final
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
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United States of America
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California
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District of Columbia
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Santa Fe
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Caba
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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/ct2/show/NCT03937219
Trial related presentations / publications
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
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Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03937219