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Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy (COSMIC-312)

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ClinicalTrials.gov Identifier: NCT03755791
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
Exelixis

Tracking Information
First Submitted Date  ICMJE November 26, 2018
First Posted Date  ICMJE November 28, 2018
Last Update Posted Date October 16, 2019
Actual Study Start Date  ICMJE December 10, 2018
Estimated Primary Completion Date August 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2019)
  • Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm [ Time Frame: Up to 25 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. ]
    Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)
  • Duration of Overall Survival (OS) for the experimental arm vs. the control arm [ Time Frame: Up to 38 months after the first subject is randomized. Defined as time from randomization to date of death from any cause. ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
  • Duration of Progression Free Survival (PFS) [ Time Frame: Up to 20 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. ]
    Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)
  • Duration of Overall Survival (OS) [ Time Frame: Up to 36 months after the first subject is randomized. Defined as time from randomization to date of death from any cause. ]
Change History Complete list of historical versions of study NCT03755791 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2019)
Duration of Progression Free Survival (PFS) for the single-agent arm vs. the control arm [ Time Frame: Up to 20 months after the first subject is randomized. ]
Duration of PFS per RECIST 1.1 by BIRC
Original Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
Objective response rate (ORR) [ Time Frame: Up to 20 months after the first subject is randomized. ]
ORR per RECIST 1.1 by BIRC
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy
Official Title  ICMJE 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
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.
Detailed Description This is a multicenter, randomized, open-label, controlled Phase 3 trial of cabozantinib in combination with atezolizumab versus sorafenib in adults with advanced HCC who have not received previous systemic anticancer therapy in the advanced HCC setting. The primary objective of this study is to evaluate the effect of cabozantinib in combination with atezolizumab on the duration of progression-free survival (PFS) and duration of overall survival (OS) versus sorafenib. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in this patient population.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Approximately 740 eligible subjects with advanced HCC will be randomized in a 2:1:1 ratio. Experimental arm (approximately 370 subjects) will receive cabozantinib plus atezolizumab. Control arm (approximately 185 subjects) will receive sorafenib. Single-agent cabozantinib arm (approximately 185 subjects) will receive single-agent cabozantinib
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: Cabozantinib
    Supplied as 20-mg tablets; administered orally daily at 40 mg
    Other Names:
    • XL184
    • Cabometyx®
  • Drug: Cabozantinib
    Supplied as 60-mg tablets; administered orally once daily at 60 mg
    Other Names:
    • XL184
    • Cabometyx®
  • Drug: Sorafenib
    Supplied as 200-mg tablets; administered orally twice daily at 400 mg
    Other Name: Nexavar®
  • Drug: Atezolizumab
    Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
    Other Name: Tecentriq®
Study Arms  ICMJE
  • Experimental: Experimental arm
    Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w
    Interventions:
    • Drug: Cabozantinib
    • Drug: Atezolizumab
  • Active Comparator: Control arm
    Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)
    Intervention: Drug: Sorafenib
  • Single-Agent Cabozantinib arm
    Subjects with advanced HCC will receive cabozantinib 60 mg qd
    Intervention: Drug: Cabozantinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 4, 2019)
740
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2018)
640
Estimated Study Completion Date  ICMJE December 1, 2021
Estimated Primary Completion Date August 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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 must be completed ≥ 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Exelixis Clinical Trials 1-888-EXELIXIS (888-393-5494) druginfo@exelixis.com
Contact: Backup or International 650-837-7400
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Canada,   Colombia,   Czechia,   France,   Georgia,   Hong Kong,   Hungary,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   New Zealand,   Philippines,   Poland,   Russian Federation,   Singapore,   Spain,   Switzerland,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03755791
Other Study ID Numbers  ICMJE XL184-312
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Exelixis
Study Sponsor  ICMJE Exelixis
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Exelixis
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP