Clinical Trials /

Atezolizumab/Bevacizumab Followed by On-demand TACE or Initial Synchronous Treatment With TACE and Atezolizumab/Bevacizumab

NCT04224636

Description:

Aim of the study is to evaluate the efficacy of up-front atezolizumab/ bevacizumab (Atezo/Bev) followed by on-demand selective transarterial chemoembolization (sdTACE) and of initial synchronous treatment with TACE and Atezo/Bev in the treatment of unresectable HCC patients.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab/Bevacizumab Followed by On-demand TACE or Initial Synchronous Treatment With TACE and Atezolizumab/Bevacizumab
  • Official Title: A Randomized, 2-arm Non-comparative Phase II Study on the Efficacy of Atezolizumab and Roche Bevacizumab (Atezo/Bev) Followed by On-demand Selective TACE (sdTACE) Upon Detection of Disease Progression or of Initial Synchronous Treatment With TACE and Atezo/Bev on 24-months Survival Rate in the Treatment of Unresectable Hepatocellular Carcinoma Patients

Clinical Trial IDs

  • ORG STUDY ID: AIO-HEP-0418
  • SECONDARY ID: 2019-002430-36
  • NCT ID: NCT04224636

Conditions

  • Hepatocellular Carcinoma Non-resectable

Purpose

Aim of the study is to evaluate the efficacy of up-front atezolizumab/ bevacizumab (Atezo/Bev) followed by on-demand selective transarterial chemoembolization (sdTACE) and of initial synchronous treatment with TACE and Atezo/Bev in the treatment of unresectable HCC patients.

Trial Arms

NameTypeDescriptionInterventions
Up-front Atezo/Bev, then TACEExperimentalPatients will receive atezolizumab and bevacizumab iv every three weeks for up to 24 months. Upon detection of at least one unequivocal progressive hepatic lesion, selective TACE directed against progressive lesion(s) (sdTACE) will be performed. RFA or MWA are permitted as alternative to TACE to treat one or more lesion that cannot be reasonably selectively targeted by TACE
    Atezo/Bev combined with TACEExperimentalFirst TACE will be performed as selectively as possible against all viable tumor lesions. Atezo/Bev will be initiated within three days from TACE. Upon detection of at least one unequivocal progressive hepatic lesion, treatment with Atezo/Bev will be continued if RFA or MWA can be used to treat this/these progressive lesion.

      Eligibility Criteria

              Key Inclusion Criteria
      
                1. Patient's signed informed consent
      
                2. Age ≥18 years at time of signing Informed Consent Form
      
                3. Ability to comply with the study protocol, according to investigator's judgement
      
                4. Life expectancy of at least 12 weeks
      
                5. HCC with histologically confirmed diagnosis
      
                6. Disease that is not amenable to curative surgical and/or local ablation but eligible
                   for TACE
      
                7. ECOG Performance Status of 0 or 1
      
                8. Child-Pugh class A or B7
      
                9. Adequate hematologic and end-organ function
      
               10. Negative HIV test at screening
      
              Key Exclusion Criteria
      
                1. Diffuse HCC or presence of vascular invasion or extrahepatic spread or more than 7
                   lesions or at least one lesion >= 7 cm
      
                2. Clinically relevant ascites
      
                3. Uncontrolled pleural effusion or pericardial effusion
      
                4. History or presence of hepatic encephalopathy
      
                5. Co-infection of HBV and HCV
      
                6. Patients on a liver transplantation list.
      
                7. Prior systemic therapy for HCC
      
                8. Prior treatment with TACE or selective internal radiation treatment (SIRT)
      
                9. Any condition representing a contraindication to TACE
      
               10. Major gastrointestinal bleeding within 4 weeks prior to randomization, untreated or
                   incompletely treated varices with bleeding or high-risk for bleeding.
      
               11. Active or history of autoimmune disease or immune deficiency
      
               12. Prior allogeneic stem cell or solid organ transplantation
      
               13. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
                   obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
                   active pneumonitis on screening chest computed tomography (CT) scan
      
               14. Active tuberculosis
      
               15. Severe infection requiring antibiotics within 4 weeks prior to randomization
      
               16. Significant cardiovascular disease
      
               17. History of congenital long QT syndrome or corrected QT interval >500 ms at screening
                   ECG
      
               18. Inadequately controlled arterial hypertension or prior history of hypertensive crisis
                   or hypertensive encephalopathy
      
               19. Significant vascular disease including aortic aneurysm requiring surgical repair or
                   peripheral arterial thrombosis with 6 months prior to randomization
      
               20. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or
                   intra-abdominal abscess within 6 months prior to randomization.
      
               21. History or clinical signs of gastrointestinal obstruction or requirement for routine
                   parenteral hydration, parenteral nutrition, or tube feeding. Evidence of abdominal
                   free air that is not explained by paracentesis or recent surgical procedure
      
               22. History of intra-abdominal inflammatory process within 6 months prior to
                   randomization, including but not limited to peptic ulcer disease, diverticulitis, or
                   colitis
      
               23. Evidence of bleeding diathesis or significant coagulopathy
      
               24. 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.
      
               25. Uncontrolled tumor-related pain. Patients requiring pain medication must be on a
                   stable regimen at enrollment.
      
               26. Severe, non healing or dehisced wound, active ulcer, or untreated bone fracture
      
               27. History of malignancy other than HCC, with the exception of patients who have been
                   disease-free for at least five years before enrollment or patients with adequately
                   treated and completely resected basal cell or squamous cell skin cancer, in situ
                   cervical, breast or prostate cancer, stage I uterine cancer
      
               28. Current or recent (within 10 days of randomization) use of acetylsalicyclic acid or
                   treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
      
               29. Current or recent (within 10 days prior to randomization) use of full dose oral or
                   parenteral anticoagulants or thrombolytic agents for therapeutic purpose.
      
               30. Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID). Occasional
                   use of NSAIDs for the symptomatic relief of medical conditions such as headache or
                   fever is allowed.
      
               31. Treatment with a live, attenuated vaccine within 4 weeks prior to randomization, or
                   anticipation of need for such a vaccine during atezolizumab treatment or within 5
                   months after the last dose of atezolizumab
      
               32. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
                   anti-CTLA-4, anti-PD-1, and antiPD-L1 therapeutic antibodies
      
               33. Hypersensitivity to atezolizumab or bevacizumab or any of the excipients, known
                   hypersensitivity to Chinese hamster ovary cell products, known hypersensitivity to
                   human or humanized antibodies
      
               34. Treatment with systemic immunostimulatory agents (including, but not limited to,
                   interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug
                   (whichever is longer) prior to randomization
      
               35. Treatment with systemic immunosuppressive medication within 2 weeks prior to
                   randomization, or anticipation of need for systemic immunosuppressive medication
                   during study treatment, with the following exceptions:
      
                   Patients who received acute, low-dose systemic immunosuppressant medication or a
                   one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of
                   corticosteroids for a contrast allergy) are eligible.
      
                   Inhaled corticosteroids for chronic obstructive pulmonary disease or bronchial asthma,
                   supplemental mineralocorticosteroids or low-dose corticosteroids for adrenalcortical
                   insufficiency are allowed.
      
               36. Major surgical procedure other than for diagnosis, open biopsy, or significant
                   traumatic injury within 28 days prior to randomization, or abdominal surgery,
                   abdominal interventions or significant abdominal traumatic injury within 60 days prior
                   to randomization or anticipation of need for major surgical procedure during the
                   course of the study or non-recovery from side effects of any such procedure
      
               37. Core biopsy or other minor surgical procedure, excluding placement of a vascular
                   access device, within 3 days prior to the first dose of bevacizumab
      
               38. Pregnant or breastfeeding females
      
               39. Participation in a clinical trial or experimental drug treatment within 28 days prior
                   to inclusion in the clinical trial or within a period of 5 half-lives of the
                   substances administered in a clinical trial or during an experimental drug treatment
                   prior to inclusion in the clinical trial, depending on which period is longest, or
                   simultaneous participation in another clinical trial while taking part in this
                   clinical trial.
      
               40. Patient committed to an institution by virtue of an order issued either by the
                   judicial or the administrative authorities
      
               41. Patient possibly dependent from the investigator including the spouse, children and
                   close relatives of any investigator
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:24-months survival rate
      Time Frame:24 months
      Safety Issue:
      Description:Percentage of patients alive after 24 months since randomization

      Secondary Outcome Measures

      Measure:Median overall survival (mOS)
      Time Frame:24 months
      Safety Issue:
      Description:Defined as the time from treatment initiation until death
      Measure:Progression-free survival (PFS)
      Time Frame:24 months
      Safety Issue:
      Description:Progression is defined according RECIST 1.1 and mRECIST
      Measure:Overall response rate (ORR)
      Time Frame:24 months
      Safety Issue:
      Description:Response is defined by RECIST 1.1 and mRECIST
      Measure:Complete response rate (CRR)
      Time Frame:24 months
      Safety Issue:
      Description:Defined by the percentage of patients with disappearance of tumor manifestation at radiological evaluation
      Measure:Disease control rate (DCR)
      Time Frame:24 months
      Safety Issue:
      Description:Defined as the percentage of patients who have achieved complete response, partial response and stable disease
      Measure:Time to deterioration of liver function
      Time Frame:24 months
      Safety Issue:
      Description:Defined as time from randomization to worsening of CTCAE grade for any of these parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, and international normalized ratio (INR)
      Measure:Time to untreatable progression
      Time Frame:24 months
      Safety Issue:
      Description:defined as time from randomization to progression not amenable to local treatment as per protocol, occurrence of vascular invasion or of extrahepatic spread, worsening of liver function to Child-Pugh score 8 or higher
      Measure:Time to stage-progression
      Time Frame:24 months
      Safety Issue:
      Description:Defined as time from randomization to disease progression to BCLC C stage
      Measure:Time to first TACE (arm A)
      Time Frame:24 months
      Safety Issue:
      Description:Defined as time from randomization to disease to the first TACE
      Measure:Quality of life (QOL)
      Time Frame:24 months
      Safety Issue:
      Description:Standardized assessment will be performed by using EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire 30 items
      Measure:Quality of life (QOL)
      Time Frame:24 months
      Safety Issue:
      Description:Standardized assessment will be performed by using EORTC QLQ-HCC18 - European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire - Hepatocellular carcinoma module 18
      Measure:Adverse Events
      Time Frame:24 months
      Safety Issue:
      Description:Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Ludwig-Maximilians - University of Munich

      Last Updated

      October 26, 2020