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Trial record 1 of 1 for:    NCT04102098
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A Study of Atezolizumab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation (IMbrave050)

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ClinicalTrials.gov Identifier: NCT04102098
Recruitment Status : Recruiting
First Posted : September 25, 2019
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the efficacy and safety of adjuvant therapy with atezolizumab plus bevacizumab compared with active surveillance in participants with completely resected or ablated hepatocellular carcinoma (HCC) who are at high risk for disease recurrence.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 662 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Open-Label Study of Atezolizumab (Anti-PD-L1 Antibody) Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation
Actual Study Start Date : December 31, 2019
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : July 31, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A (atezolizumab plus bevacizumab)
Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.
Drug: Atezolizumab
Atezolizumab 1200 mg will be administered by IV infusion on Day 1 of each 21-day cycle.
Other Name: Tecentriq

Drug: Bevacizumab
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
Other Name: Avastin

No Intervention: Arm B (active surveillance)
Active surveillance of participants.



Primary Outcome Measures :
  1. Recurrence-Free Survival (RFS), as Determined by IRF [ Time Frame: Baseline up to approximately 39 months ]
    RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by an IRF, or death from any cause (whichever occurs first).


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Baseline up to approximately 91 months ]
    OS is defined as the time from randomization to death from any cause.

  2. RFS as Determined by the Investigator [ Time Frame: Baseline up to approximately 91 months ]
    RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by an investigator, or death from any cause (whichever occurs first).

  3. Time to Recurrence (TTR) [ Time Frame: Baseline up to approximately 91 months ]
    TTR defined as the time from randomization to first documented occurrence of local, regional, or etastatic HCC, as determined by the investigator and by an IRF.

  4. RFS Rate at 24 and 36 Months, as Assessed by the IRF [ Time Frame: Randomization up to 24 months and up to 36 months ]
  5. RFS Rate at 24 and 36 Months, as Assessed by the Investigator [ Time Frame: Randomization up to 24 months and up to 36 months ]
  6. OS Rate at 24 and 36 Months [ Time Frame: Baseline to 24 and 36 months ]
    OS rate defined as the proportion of patients who have not experienced death from any cause at 24 and 36 months after randomization.

  7. Time to Extrahepatic Spread (EHS) or Macrovascular Invasion [ Time Frame: Baseline up to approximately 91 months ]
    Time to EHS or macrovascular invasion after randomization, defined as the time from randomization to the first appearance of EHS or macrovascular invasion, as determined by the investigator.

  8. RFS in Pd-L1-High Subgroup [ Time Frame: Baseline up to approximately 91 months ]
    RFS after randomization as determined by the investigator and by an IRF, among patients in the PD-L1-high subgroup.

  9. Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 91 months ]
  10. Serum Concentration of Atezolizumab [ Time Frame: Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16 (each cycle is 21 days) ]
  11. Number of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16 (each cycle is 21 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Participants with a first diagnosis of HCC who have undergone a curative resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only)
  • Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA only)
  • Absence of major macrovascular invasion (except Vp1/Vp2) and extrahepatic spread
  • Full recovery from surgical resection or ablation within 4 weeks prior to randomization
  • High risk for HCC recurrence after resection or ablation
  • For patients who received post-operative transarterial chemoembolization: full recovery from the procedure within 4 weeks prior to randomization
  • For patients with resected HCC, availability of a representative baseline tumor tissue sample
  • ECOG Performance Status of 0 or 1
  • Child-Pugh Class A status
  • Adequate hematologic and end-organ function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
  • Recurrent HCC prior to randomization
  • Evidence of residual, recurrent, or metastatic disease at randomization
  • Clinically significant ascites
  • History of hepatic encephalopathy
  • Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
  • Have received more than 1 cycle of adjuvant TACE following surgical resection
  • 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 CT scan
  • Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina
  • 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
  • Active tuberculosis
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to Day 1 of Cycle 1.
  • Co-infection with HBV and HCV.
  • Uncontrolled or symptomatic hypercalcemia
  • Any treatment for HCC prior to resection or ablation, including systemic therapy and locoregional therapy such as TACE
  • Treatment with systemic immunostimulatory or immunosuppressive agents
  • Inadequately controlled arterial hypertension
  • History of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease
  • Evidence of bleeding diathesis or significant coagulopathy
  • Current or recent use of aspirin or full-dose oral or parenteral anticoagulants
  • Core biopsy within 3 days of Day 1 of Cycle 1
  • History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess
  • Serious non-healing or dehiscing wound
  • Major surgical procedure within four weeks
  • Chronic daily treatment with a non-steroidal anti-inflammatory drug

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): NCT04102098


Contacts
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Contact: Reference Study ID Number: WO41535 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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04102098    
Other Study ID Numbers: WO41535
2019-002491-14 ( EudraCT Number )
First Posted: September 25, 2019    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: June 2020
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.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study 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: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Disease Attributes
Pathologic Processes
Bevacizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors