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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 : December 7, 2018
Sponsor:
Information provided by (Responsible Party):
Exelixis

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. An exploratory 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. An exploratory objective is to evaluate the single-agent activity and safety of cabozantinib in this patient population.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Approximately 640 eligible subjects with advanced HCC will be randomized in a 6:3:1 ratio. Experimental arm (approximately 384 subjects) will receive cabozantinib plus atezolizumab. Control arm (approximately 192 subjects) will receive sorafenib. Exploratory arm (approximately 64 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
Estimated Study Start Date : December 1, 2018
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine


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®

Exploratory 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®




Primary Outcome Measures :
  1. 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)

  2. 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. ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Up to 20 months after the first subject is randomized. ]
    ORR per RECIST 1.1 by BIRC



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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.
  • 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:

  • 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

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

Locations
United States, California
Exelixis Clinical Site #2 Recruiting
Rialto, California, United States, 92377
Contact: Exelixis    888-393-5494    druginfo@exelixis.com   
United States, Nevada
Exelixis Clinical Site #1 Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Exelixis    888-393-5494    druginfo@exelixis.com   
Sponsors and Collaborators
Exelixis

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT03755791     History of Changes
Other Study ID Numbers: XL184-312
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018

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:
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
Niacinamide
Antibodies, Monoclonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Immunologic Factors