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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/NCT03755791




Registration number
NCT03755791
Ethics application status
Date submitted
26/11/2018
Date registered
28/11/2018
Date last updated
22/03/2024

Titles & IDs
Public title
Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy
Scientific title
A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy
Secondary ID [1] 0 0
XL184-312
Universal Trial Number (UTN)
Trial acronym
COSMIC-312
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabozantinib
Treatment: Drugs - Cabozantinib
Treatment: Drugs - Sorafenib
Treatment: Drugs - Atezolizumab

Experimental: Experimental arm - Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w

Active Comparator: Control arm - Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)

Other: Single-Agent Cabozantinib arm - Subjects with advanced HCC will receive cabozantinib 60 mg qd


Treatment: Drugs: Cabozantinib
Supplied as 20-mg tablets; administered orally daily at 40 mg

Treatment: Drugs: Cabozantinib
Supplied as 60-mg tablets; administered orally once daily at 60 mg

Treatment: Drugs: Sorafenib
Supplied as 200-mg tablets; administered orally twice daily at 400 mg

Treatment: Drugs: Atezolizumab
Supplied as 1200 mg/20 mL (60 mg/mL) in sing-dose vials; administered as an IV infusion once every 3 weeks (q3w).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm
Timepoint [1] 0 0
Up to 27 months after the first subject is randomized. Defined as time from randomization to the earlier of progressive disease (PD) per RECIST 1.1 as determined by the Blinded Independent Radiology Committee (BIRC) or death from any cause.
Primary outcome [2] 0 0
Duration of Overall Survival (OS) for the experimental arm vs. the control arm
Timepoint [2] 0 0
Up to 36 months after the first subject is randomized. Defined as time from randomization to date of death from any cause.
Secondary outcome [1] 0 0
Duration of Progression Free Survival (PFS) for the single-agent arm vs. the control arm
Timepoint [1] 0 0
Up to 20 months after the first subject is randomized.

Eligibility
Key inclusion criteria
- Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic
patients by CT or MRI per the AASLD 2018 or EASL 2018 guidelines.

- The subject has disease that is not amenable to a curative treatment approach (eg,
transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).

- Measurable disease per RECIST 1.1 as determined by the Investigator.

- Barcelona Clinic Liver Cancer (BCLC) stage Category B or C.

- Child-Pugh Score of A.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular
cholangiocarcinoma.

- Prior systemic anticancer therapy for advanced HCC including but not limited to
chemotherapy, small molecule kinase inhibitors, and immune checkpoint inhibitors
(ICIs). Subjects who have received local intratumoral or arterial chemotherapy are
eligible; local anticancer therapy within = 28 days before randomization

- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy
within 8 weeks prior to randomization.

- Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks
prior to randomization.

- Concomitant anticoagulation with oral anticoagulants

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
Open (masking not used)
Who is / are masked / blinded?



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
10/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
837
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Exelixis Clinical Site #78 - Camperdown
Recruitment hospital [2] 0 0
Exelixis Clinical Site #165 - Darlinghurst
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Exelixis Clinical Site #171 - Kingswood
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Exelixis Clinical Site #126 - Kogarah
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Exelixis Clinical Site #155 - Westmead
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Exelixis Clinical Site #142 - Greenslopes
Recruitment hospital [7] 0 0
Exelixis Clinical Site #17 - Kurralta Park
Recruitment hospital [8] 0 0
Exelixis Clinical Site #107 - Box Hill
Recruitment hospital [9] 0 0
Exelixis Clinical Site #166 - Heidelberg
Recruitment hospital [10] 0 0
Exelixis Clinical Site #72 - Parkville
Recruitment hospital [11] 0 0
Exelixis Clinical Site #190 - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
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2010 - Darlinghurst
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2747 - Kingswood
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2217 - Kogarah
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2145 - Westmead
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4120 - Greenslopes
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- Kurralta Park
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3128 - Box Hill
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3084 - Heidelberg
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3050 - Parkville
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6009 - Nedlands
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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 Phase 3 study evaluates the safety and efficacy of cabozantinib in combination with
atezolizumab versus the standard of care sorafenib in adults with advanced hepatocellular
carcinoma (HCC) who have not received previous systemic anticancer therapy. A single-agent
cabozantinib arm will be enrolled in which subjects receive single agent cabozantinib in
order to determine its contribution to the overall safety and efficacy of the combination
with atezolizumab.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03755791
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/NCT03755791