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Trial record 1 of 1 for:    03755791
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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 : May 18, 2022
Sponsor:
Information provided by (Responsible Party):
Exelixis

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Cabozantinib Drug: Sorafenib Drug: Atezolizumab Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 740 participants
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
Official 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
Actual Study Start Date : June 10, 2018
Actual Primary Completion Date : March 8, 2021
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Experimental arm
Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w
 Drug: Cabozantinib
Supplied as 20-mg tablets; administered orally daily at 40 mg
Other Names:
  • XL184
  • Cabometyx®

Drug: Atezolizumab
Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
Other Name: Tecentriq®
Active Comparator: Control arm
Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)
 Drug: Sorafenib
Supplied as 200-mg tablets; administered orally twice daily at 400 mg
Other Name: Nexavar®
Single-Agent Cabozantinib arm
Subjects with advanced HCC will receive cabozantinib 60 mg qd
 Drug: Cabozantinib
Supplied as 60-mg tablets; administered orally once daily at 60 mg
Other Names:
  • XL184
  • Cabometyx®


Outcome Measures
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Primary Outcome Measures :
  1. 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)

  2. 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. ]

Secondary Outcome Measures :
  1. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03755791


Contacts
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Contact: Exelixis Clinical Trials 1-888-EXELIXIS (888-393-5494) druginfo@exelixis.com
Contact: Backup or International 650-837-7400

Locations
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Sponsors and Collaborators
Exelixis
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT03755791    
Other Study ID Numbers: XL184-312
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Exelixis:
liver
cancer
hepatocellular
carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
 Digestive System Diseases
Liver Diseases
Sorafenib
Atezolizumab
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action