Clinical Trials /

Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

NCT03298451

Description:

This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
  • Official Title: A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: D419CC00002
  • NCT ID: NCT03298451

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Arm 1
Tremelimumab (Regimen 1)Arm 2
Tremelimumab (Regimen 2)Arm 3
SorafenibArm 4
Durvalumab (Regimen 1)Arm 2
Durvalumab (Regimen 2)Arm 3

Purpose

This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy.

Detailed Description

      The study population includes patients 18 years of age or older with advanced HCC, Barcelona
      Clinic Liver Cancer stage B not eligible for locoregional therapy or stage C, and Child-Pugh
      A classification liver disease. Patients must not have received any prior systemic therapy
      for unresectable HCC.

      Patients in all treatment arms may continue receiving their originally assigned treatment, at
      the Investigator's discretion, until progression

      Patients in all arms with confirmed PD who, in the Investigator's opinion, continue to
      receive benefit from their assigned treatment and meet the criteria for treatment in the
      setting of PD may continue to receive their assigned treatment.

      If a patient discontinues study drug(s) due to disease progression, the patient will enter
      survival follow-up. Patients who have discontinued treatment due to toxicity or symptomatic
      deterioration or who have commenced subsequent anticancer therapy, will have tumor
      assessments until confirmed PD and will be followed for survival.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalDurvalumab
  • Durvalumab
Arm 2ExperimentalDurvalumab in combination with tremelimumab (Regimen 1)
  • Tremelimumab (Regimen 1)
  • Durvalumab (Regimen 1)
Arm 3ExperimentalDurvalumab in combination with tremelimumab (Regimen 2)
  • Tremelimumab (Regimen 2)
  • Durvalumab (Regimen 2)
Arm 4Active ComparatorSorafenib
  • Sorafenib

Eligibility Criteria

        Inclusion criteria

          -  HCC based on histopathological confirmation

          -  No prior systemic therapy for HCC

          -  Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional
             therapy) or stage C

          -  Child-Pugh Score class A

          -  ECOG performance status of 0 or 1 at enrollment

        Exclusion criteria

          -  Hepatic encephalopathy within past 12 months or requirement for medication to prevent
             or control encephalopathy

          -  Clinically meaningful ascites

          -  Main portal vein tumor thrombosis

          -  Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding)
             within 12 months

          -  HBV and HVC co-infection, or HBV and Hep D co-infection
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:From the date of randomization until death due to any cause, assessed up to 4 years.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time to Progression (TTP)
Time Frame:From randomization until objective tumor progression, assessed up to 4 years.
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:From date of randomization until the date of objective disease progression or death, assessed up to 4 years.
Safety Issue:
Description:
Measure:Objective response rate (ORR)
Time Frame:Until progression, assessed up to 4 years.
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:Until progression, assessed up to 4 years.
Safety Issue:
Description:
Measure:Duration of response (DoR)
Time Frame:From the date of first documented response (RECIST 1.1.) until the first date of documented progression or death in the absence of disease progression, assessed up to 4 years.
Safety Issue:
Description:
Measure:Health status/quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30)
Time Frame:From randomization up to approximately 3 months from the treatment discontinuation, assessed up to 4 years.
Safety Issue:
Description:
Measure:Presence of ADA for durvalumab and tremelimumab
Time Frame:Starting prior to the first dose of the treatment up to approximately 3 months from the treatment discontinuation, assessed up to 4 years.
Safety Issue:
Description:
Measure:The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by trough concentration
Time Frame:Starting prior to the first dose of the treatment up to approximately 3 months from the treatment discontinuation, assessed up to 4 years.
Safety Issue:
Description:
Measure:Disease-related symptoms measured by EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18)
Time Frame:From randomization up to approximately 3 months from the treatment discontinuation, assessed up to 4 years.
Safety Issue:
Description:
Measure:The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by peak concentration
Time Frame:Starting prior to the first dose of the treatment up to approximately 3 months from the treatment discontinuation, assessed up to 4 years.
Safety Issue:
Description:

Details

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

Trial Keywords

  • Hepatocellular Carcinoma Non-Resectable

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