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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

NCT03755791

Description:

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.

Related Conditions:
  • Combined Hepatocellular Carcinoma and Cholangiocarcinoma
  • Fibrolamellar Carcinoma
  • Hepatocellular Carcinoma
  • Sarcomatoid Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy
  • 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

Clinical Trial IDs

  • ORG STUDY ID: XL184-312
  • NCT ID: NCT03755791

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
CabozantinibXL184, Cabometyx®Experimental arm
CabozantinibXL184, Cabometyx®Single-Agent Cabozantinib arm
SorafenibNexavar®Control arm
AtezolizumabTecentriq®Experimental arm

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental armExperimentalSubjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w
  • Cabozantinib
  • Atezolizumab
Control armActive ComparatorSubjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)
  • Sorafenib
Single-Agent Cabozantinib armOtherSubjects with advanced HCC will receive cabozantinib 60 mg qd
  • Cabozantinib

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:Duration of PFS per RECIST 1.1 by BIRC

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Exelixis

Trial Keywords

  • liver
  • cancer
  • hepatocellular
  • carcinoma

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