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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 : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Unresectable Hepatocellular Carcinoma Drug: Atezolizumab Drug: Lenvatinib Drug: Sorafenib Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 554 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 26, 2021
Estimated Primary Completion Date : October 8, 2024
Estimated Study Completion Date : October 8, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. Percentage of Participants With Adverse Events [ Time Frame: Throughout study duration (approximately 42 months) ]
  7. 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) ]
  8. Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Throughout study (approximately 42 months) ]
  9. Serum Concentration of Atezolizumab [ Time Frame: At pre-defined intervals from first administration of study drug to approximately 42 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT04770896


Contacts
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Contact: Reference Study ID Number: MO42541 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04770896    
Other Study ID Numbers: MO42541
First Posted: February 25, 2021    Key Record Dates
Last Update Posted: July 8, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
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).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action