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

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ClinicalTrials.gov Identifier: NCT03434379
Recruitment Status : Recruiting
First Posted : February 15, 2018
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Atezolizumab Drug: Bevacizumab Drug: Sorafenib Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 480 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 in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Actual Study Start Date : March 15, 2018
Estimated Primary Completion Date : May 25, 2021
Estimated Study Completion Date : June 29, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Atezolizumab + Bevacizumab
Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator
Drug: Atezolizumab
Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle

Drug: Bevacizumab
Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21 day cycle

Active Comparator: Sorafenib
Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator
Drug: Sorafenib
Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Baseline to death from any cause, through the end of study (up to approximately 4 years) ]
  2. Objective Response (OR) defined as complete response or partial response as determined by the Investigator according to RECIST V1.1 [ Time Frame: Baseline until disease progression or death from any cause, whichever occurs first. Following initiation of study treatment, assessed at baseline, every 6 weeks for first 54 weeks, and every 9 weeks thereafter (up to approximately 4 years) ]

Secondary Outcome Measures :
  1. Progression Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline until disease progression or death from any cause, whichever occurs first. Following initiation of study treatment, assessed at baseline, every 6 weeks for first 54 weeks, and every 9 weeks thereafter (up to approximately 4 years) ]
  2. Time to Progression (TTP) as Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline to first occurance of disease progression. Following initiation of study treatment, assessed at baseline, every 6 weeks for first 54 weeks, and every 9 weeks thereafter (up to approximately 4 years) ]
  3. 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) ]
  4. OR as Determined by an Independent Review Facility (IRF) According to Response Evaluation Criteria in Solid Tumors, v1.1 (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 (Approximately 4 years) ]
  5. PFS as Determined by an IRF According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death from any cause (whichever occurs first), through the end of study (Approximately 4 years) ]
  6. TTP as Determined by an IRF According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death from any cause (whichever occurs first), through the end of study (up to approximately 4 years) ]
  7. 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) ]
  8. OR as Determined by an IRF According to Hepatocellular Carcinoma Modified RECIST (HCC mRECIST) [ 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) ]
  9. PFS Determined by an IRF According to HCC mRECIST [ Time Frame: Baseline to first occurrence of disease progression or death from any cause (whichever occurs first), through the end of study (up to approximately 4 years) ]
  10. TTP as Determined by an IRF According to HCC mRECIST [ Time Frame: Baseline to first occurrence of disease progression or death from any cause (whichever occurs first), through the end of study (up to approximately 4 years) ]
  11. 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) ]
  12. Time to Deterioration (TTD) in Patient-Reported HRQoL/GHS, 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: Baseline to first deterioration maintained for two consecutive timepoints, or one timepoint followed by death (from any cause) within 3 weeks from any cause, through 1 year after treatment discontinuation ]
  13. OR 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) ]
  14. Serum Concentration of Atezolizumab [ Time Frame: Day 1 cycle 1, prior to infusion and 30 minutes post-infusion; Day 1 of cycles 2 and 4 prior to infusion; at treatment discontinuation, through end of study (Approximately 4 years) ]
  15. Change from Baseline in Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Baseline to first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 4 years) ]
  16. Percentage of Participants with Adverse Events [ Time Frame: Baseline to end of study (approximately 4 years) ]
  17. OR as Determined by an IRF According to RECIST v1.1 [ Time Frame: Baseline Serum AFP Level (< 400 ng/mL or >/=400 ng/mL) ]
  18. OS [ Time Frame: Baseline Serum AFP Level (< 400 ng/mL or >/= 400 ng/mL) ]


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

Inclusion Criteria:

  • Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)
  • No prior systemic therapy for HCC
  • 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
  • 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
  • Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding
  • 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
  • Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)

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): NCT03434379


Contacts
Contact: Reference Study ID Number: YO40245 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03434379     History of Changes
Other Study ID Numbers: YO40245
2017-003691-31 ( EudraCT Number )
First Posted: February 15, 2018    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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
Bevacizumab
Sorafenib
Atezolizumab
Niacinamide
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Immunologic Factors