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A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab (IMbrave251)

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ClinicalTrials.gov Identifier: NCT04770896
Recruitment Status : Recruiting
First Posted : February 25, 2021
Last Update Posted : January 18, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE February 23, 2021
First Posted Date  ICMJE February 25, 2021
Last Update Posted Date January 18, 2022
Actual Study Start Date  ICMJE April 26, 2021
Estimated Primary Completion Date October 8, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2021)
Overall Survival (OS) [ Time Frame: Randomization until death from any cause (approximately 42 months) ]
Overall survival (OS) is defined as the time from randomization into the study to death from any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2021)
  • Progression Free Survival (PFS) [ Time Frame: Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months) ]
    Progression free survival (PFS) is defined as the time from randomization into the study to the first occurrence of disease progression or death from any cause (whichever occurs first).
  • Confirmed Objective Response Rate (ORR) [ Time Frame: Approximately 42 months ]
    Confirmed Objective Response Rate (ORR) is defined as the proportion of patients with a best response of either complete or partial response.
  • Time to Progression (TTP) [ Time Frame: Randomization until the first occurrence of disease progression (approximately 42 months) ]
    Time to Progression (TTP) is defined as the time from randomization to the first occurrence of disease progression.
  • Duration of Response (DOR) [ Time Frame: Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months) ]
    Duration of Response (DOR) is defined as the time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause (whichever occurs first).
  • Time to deterioration (TTD) [ Time Frame: Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months) ]
    Time to deterioration (TTD) is defined as the time from randomization to first deterioration (decrease from baseline of ≥ 10 points) maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks (if Cycle 1-6) or 6 weeks (if after Cycle 6) in the following European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30(EORTC QLQC30) scales (separately): physical function, role function, and GHS/QoL.
  • Percentage of Participants With Adverse Events [ Time Frame: Throughout study duration (approximately 42 months) ]
  • Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events [ Time Frame: Throughtout study (approximately 42 months) ]
  • Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Throughout study (approximately 42 months) ]
  • Serum Concentration of Atezolizumab [ Time Frame: At pre-defined intervals from first administration of study drug to approximately 42 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
Official Title  ICMJE A Phase III, Open-Label, Randomized Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
Brief Summary This is a Phase III, open label, randomized, two-arm, multicenter study designed to evaluate the safety and efficacy of atezolizumab plus lenvatinib or sorafenib versus lenvatinib or sorafenib alone in locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) participants who have progressed following prior HCC treatment with atezolizumab and bevacizumab combination.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unresectable Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: Atezolizumab
    Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
    Other Name: Tecentriq
  • Drug: Lenvatinib
    Lenvatinib will be administered once daily by mouth each day of every 21-day study treatment cycle. Participants with a baseline body weight of < 60 kg will receive a daily dose of 8 mg. Participants with a baseline body weight of ≥ 60 kg will receive a daily dose of 12 mg.
  • Drug: Sorafenib
    Sorafenib will be administered at a dose of 800 mg per day, i.e. two tablets of 200 mg swallowed by mouth twice daily (equivalent to a total daily dose of 800 mg) each day of every 21-day study treatment cycle.
Study Arms  ICMJE
  • Experimental: Atezolizumab + Lenvatinib or Sorafenib
    Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Lenvatinib
    • Drug: Sorafenib
  • Active Comparator: Lenvatinib or Sorafenib
    Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
    Interventions:
    • Drug: Lenvatinib
    • Drug: Sorafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 23, 2021)
554
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 8, 2024
Estimated Primary Completion Date October 8, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
  • Disease progression following prior atezolizumab plus bevacizumab combination treatment for HCC, for at least 4 consecutive treatment cycles, or 2 subsequent tumor assessments, whichever is longer.
  • At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 7 days prior to randomization
  • Child-Pugh class A within 7 days prior to randomization
  • Adequate hematologic and end-organ function

Exclusion Criteria:

  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
  • History of leptomeningeal disease
  • History of hepatic encephalopathy, proceeding 6 months, unresponsive to therapy within 3 days
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: MO42541 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com
Listed Location Countries  ICMJE Belgium,   Brazil,   Canada,   Chile,   China,   Costa Rica,   Croatia,   Finland,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Russian Federation,   Slovenia,   Spain,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom
Removed Location Countries Austria,   Egypt,   Philippines
 
Administrative Information
NCT Number  ICMJE NCT04770896
Other Study ID Numbers  ICMJE MO42541
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP