Clinical Trials /

A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma [IMbrave150]

NCT03434379

Description:

This study will evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma [IMbrave150]
  • Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: YO40245
  • SECONDARY ID: 2017-003691-31
  • NCT ID: NCT03434379

Conditions

  • Carcinoma, Hepatocellular

Interventions

DrugSynonymsArms
AtezolizumabAtezolizumab + Bevacizumab
BevacizumabAtezolizumab + Bevacizumab
SorafenibSorafenib

Purpose

This study will evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment.

Detailed Description

      The participants will be randomized in a 2:1 ratio to one of the two treatment arms: Arm A
      (experimental arm): Atezolizumab +bevacizumab; Arm B (control arm): Sorafenib
    

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab + BevacizumabExperimentalParticipants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator
  • Atezolizumab
  • Bevacizumab
SorafenibActive ComparatorParticipants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator
  • Sorafenib

Eligibility Criteria

        Inclusion Criteria:

          -  Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)

          -  No prior systemic therapy for HCC. Previous use of herbal therapies/traditional
             Chinese medicines with anti-cancer activity included in the label is allowed, provided
             that these medications are discontinued prior to randomization.

          -  At least one measurable untreated lesion

          -  ECOG Performance Status of 0 or 1

          -  Adequate hematologic and end-organ function

          -  For women of childbearing potential: agreement to remain abstinent

          -  For men: agreement to remain abstinent

          -  Child-Pugh class A

        Exclusion Criteria:

          -  History of leptomeningeal disease

          -  Active or history of autoimmune disease or immune deficiency

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest computed tomography scan

          -  Known active tuberculosis

          -  History of malignancy other than HCC within 5 years prior to screening, with the
             exception of malignancies with a negligible risk of metastasis or death

          -  Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
             or within at least 5 months after the last dose of atezolizumab, 6 months after the
             last dose of bevacizumab, or 1 month after the last dose of sorafenib

          -  Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC

          -  Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
             high-risk for bleeding

          -  A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
             to initiation of study treatment.

          -  Moderate or severe ascites

          -  History of hepatic encephalopathy

          -  Co-infection of HBV and HCV

          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)
             metastases

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures

          -  Uncontrolled or symptomatic hypercalcemia

          -  Treatment with systemic immunostimulatory agents

          -  Inadequately controlled arterial hypertension

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  Evidence of bleeding diathesis or significant coagulopathy

          -  History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction
             including sub-occlusive disease related to the underlying disease or requirement for
             routine parenteral hydration

          -  Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture

          -  Metastatic disease that involves major airways or blood vessels, or centrally located
             mediastinal tumor masses

          -  Local therapy to liver within 28 days prior to initiation of study treatment or
             non-recovery from side effects of any such procedure

          -  Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Randomization to death from any cause, through the end of study (up to approximately 4 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response (OR) defined as complete response or partial response as determined by the Investigator according to RECIST V1.1
Time Frame:From baseline until disease progression or death, whichever occurs first (approximately 4 years)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1
Time Frame:Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Safety Issue:
Description:
Measure:Time to Progression (TTP) as Determined by an Investigator According to RECIST v1.1
Time Frame:Randomization to first occurance of disease progression (up to approximately 4 years)
Safety Issue:
Description:
Measure:Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
Time Frame:From first occurrence of a documented objective response to disease progression or death. Following initiation of study treatment, assessed at baseline, every 6 weeks for the first 54 weeks, and every 9 weeks thereafter (up to approximately 4 years)
Safety Issue:
Description:
Measure:OR defined as complete or partial response as Determined by an IRF According to RECIST v1.1
Time Frame:From baseline until disease progression or death, whichever occurs first (approximately 4 years)
Safety Issue:
Description:
Measure:TTP as Determined by an IRF According to RECIST v1.1
Time Frame:Randomization to the first occurence of disease progression through the end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:DOR as Determined by an IRF According to RECIST v1.1
Time Frame:From the first occurrence of a documented objective response until confirmed disease progression or death from any cause (whichever occurs first), through the end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:OR defined as complete or partial response, as Determined by an IRF According to Hepatocellular Carcinoma Modified RECIST (HCC mRECIST)
Time Frame:From baseline until disease progression or death, whichever occurs first (approximately 4 years)
Safety Issue:
Description:
Measure:PFS as Determined by an IRF According to HCC mRECIST
Time Frame:Randomization to first occurrence of disease progression or death from any cause (whichever occurs first), through the end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:TTP as Determined by an IRF According to HCC mRECIST
Time Frame:Randomization to first occurrence of disease progression through the end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:DOR as Determined by an IRF According to HCC mRECIST
Time Frame:Time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) through the end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:Time to Deterioration (TTD) in Patient-Reported GHS/QoL, physical functioning, and role functioning, as determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score
Time Frame:Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death (from any cause) within 3 weeks from any cause, through 1 year after treatment discontinuation
Safety Issue:
Description:
Measure:PFS as determined by the investigator according to RECIST v1.1
Time Frame:Baseline Serum Alpha-Fetoprotein (AFP) Level (< 400 ng/mL or >/=400 ng/mL)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab
Time Frame:Day 1 cycle 1, prior to infusion and 30 minutes post-infusion; Day 1 of cycles 2, 3, 4 , 8, 12 and 16 prior to infusion; at treatment discontinuation, through end of study (Approximately 4 years)
Safety Issue:
Description:
Measure:Change from Baseline in Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame:Day 1 cycle 1, prior to infusion; Day 1 of cycles 2, 3, 4 , 8, 12 and 16 prior to infusion; at treatment discontinuation, through end of study (Approximately 4 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline to end of study (approximately 4 years)
Safety Issue:
Description:
Measure:PFS as Determined by an IRF According to RECIST v1.1
Time Frame:Baseline Serum AFP Level (< 400 ng/mL or >/=400 ng/mL)
Safety Issue:
Description:
Measure:OS
Time Frame:Baseline Serum AFP Level (< 400 ng/mL or >/= 400 ng/mL)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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