The ABC-HCC Trial: Atezolizumab Plus Bevacizumab vs. Transarterial Chemoembolization (TACE) in Intermediate-stage HepatoCellular Carcinoma
NCT ID: NCT04803994
Last Updated: 2025-01-07
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
PHASE3
Total Enrollment
434 participants
Study Classification
INTERVENTIONAL
Study Start Date
2021-07-06
Study Completion Date
2027-07-31
Brief Summary
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The ABC-HCC trial is a Phase IIIb, randomised, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab plus bevacizumab versus TACE in patients with intermediate-stage HCC. Approximately 434 patients in two arms of treatment will be enrolled.
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Detailed Description
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The main purpose of this phase IIIb study is to test the efficacy and safety of atezolizumab in combination with bevacizumab compared to TACE in patients with intermediate stage liver cancer.
Primary efficacy objective is to assess the efficacy of atezolizumab in combination with bevacizumab compared to TACE in patients with intermediate stage liver cancer.
The secondary efficacy objective is to further characterize the responses obtained with the respective therapeutic strategy and to assess the impact of each therapeutic strategy on liver function over time.
Furthermore the objective is to evaluate the safety and tolerability of each therapeutic strategy and their respective impact on Quality of Life and to identify prognostic and predictive angiogenic and immune related biomarkers (tissue and circulating) for study endpoints.
This is a Phase IIIb, randomised, multicenter, open-label study. Approximately 434 patients suffering from intermediate-stage hepatocellular carcinoma will be enrolled in this trial. Patients will be recruited from up to 60 sites in 10 different countries.
Primary efficacy objective is to assess the efficacy of atezolizumab in combination with bevacizumab compared to TACE in patients with intermediate stage liver cancer.
The secondary efficacy objective is to further characterize the responses obtained with the respective therapeutic strategy and to assess the impact of each therapeutic strategy on liver function over time.
Furthermore the objective is to evaluate the safety and tolerability of each therapeutic strategy and their respective impact on Quality of Life and to identify prognostic and predictive angiogenic and immune related biomarkers (tissue and circulating) for study endpoints.
This is a Phase IIIb, randomised, multicenter, open-label study. Approximately 434 patients suffering from intermediate-stage hepatocellular carcinoma will be enrolled in this trial. Patients will be recruited from up to 60 sites in 10 different countries.
Conditions
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Hepatocellular Carcinoma
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Clinical trial with two study arms:
Experimental arm A: 50% of the patients will receive a combination therapy (systemic) of the monoclonal antibodies atezolizumab and bevacizumab.
Control arm B: 50% of the patients will receive TACE therapy (locoregional).
Experimental arm A: 50% of the patients will receive a combination therapy (systemic) of the monoclonal antibodies atezolizumab and bevacizumab.
Control arm B: 50% of the patients will receive TACE therapy (locoregional).
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Systemic therapy with atezolizumab + bevacizumab
Patients receive atezolizumab 1200 mg flat dose plus bevacizumab 15 mg/kg given intravenously every 3 weeks until failure of strategy, participant request, or withdrawal of consent for a maximum of up to 24 months.
The discontinuation of one of the study drugs for toxicity reasons does not qualify as failure of treatment strategy as long as the other drug can be continued according to protocol.
Group Type
EXPERIMENTAL
Atezolizumab
Intervention Type
DRUG
1200 mg atezolizumab intravenously Q3W (max 32 cycles, up to 24 months)
Bevacizumab
Intervention Type
DRUG
15 mg/kg intravenously Q3W (max 32 cycles, up to 24 months)
Locoregional therapy with TACE
Patients will receive initial TACE and - if required to achieve or improve an objective response - a second TACE after 8 weeks (±7 days window). Thereafter, additional TACE can be applied on demand until failure of strategy, participant request, or withdrawal of consent for a maximum of up to 24 months.
TACE must be discontinued in cases of technical difficulties making additional TACE impossible.
Only conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) approaches are accepted as TACE therapy. However, consistency in the TACE procedure and the use of the chemotherapeutic agent has to be maintained for each individual patient.
Group Type
ACTIVE_COMPARATOR
TACE
Intervention Type
PROCEDURE
Locoregional therapy will be performed as a standard-of-care procedure
Interventions
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Atezolizumab
1200 mg atezolizumab intravenously Q3W (max 32 cycles, up to 24 months)
Intervention Type
DRUG
Bevacizumab
15 mg/kg intravenously Q3W (max 32 cycles, up to 24 months)
Intervention Type
DRUG
TACE
Locoregional therapy will be performed as a standard-of-care procedure
Intervention Type
PROCEDURE
Other Intervention Names
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Tecentriq
Avastin
transarterial chemoembolization
Eligibility Criteria
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Inclusion Criteria
1. Signed Informed Consent Form available
2. Patients\* ≥ 18 years of age at time of signing Informed Consent Form
3. Confirmed hepatocellular carcinoma diagnosis based on histopathological findings from tumor tissue or typical diagnostic imaging on dynamic CT or MRI according to AASLD criteria.
4. Intermediate stage HCC as defined by the following criteria:
* Disease not amenable to curative surgery, liver transplantation or curative ablation BUT disease amenable to TACE at enrollment as judged by the investigator.
* No massive multinodular pattern preventing adequate TACE
* No tumor of a diffuse infiltrative HCC type (hypovascular infiltrative tumors with ill-defined borders)
* Patent portal vein flow
12. Patients with seizure disorder requiring medication.
13. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
14. Evidence or history of bleeding diathesis or any hemorrhage or bleeding event \> CTCAE grade 3 within 4 weeks prior to randomization.
15. Non-healing wound, ulcer, or bone fracture.
16. Renal failure requiring hemo- or peritoneal dialysis.
17. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation including a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein; known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation.
18. Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), with the following exception: patients with a positive HIV test at screening are eligible, provided they are stable on anti-retroviral therapy, have a CD4 count \> 200 cells/µL, and have an undetectable viral load.
19. Active tuberculosis
20. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
21. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan Note: History of radiation pneumonitis within the radiation field (fibrosis) is permitted.
22. Persistent proteinuria of CTCAE Grade 3 or higher (\> 3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).
23. Pregnant or nursing women
24. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
25. Active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
Note: History of autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone, or controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible based on consultation with the sponsor's medical monitor. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
26. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, 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 for the study.
* Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
27. Use of any herbal remedies known to interfere with the liver or other major organ functions. Patients must notify the investigator of all herbal remedies used during the study.
28. Administration of a live, attenuated vaccine within four weeks prior to start of enrollment, or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last TACE procedure.
29. History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Other similar cases can be considered after discussion with lead investigators and sponsor.
30. Receipt of an investigational drug within 28 days prior to initiation of study drug
31. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent or patients with substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
2. Patients\* ≥ 18 years of age at time of signing Informed Consent Form
3. Confirmed hepatocellular carcinoma diagnosis based on histopathological findings from tumor tissue or typical diagnostic imaging on dynamic CT or MRI according to AASLD criteria.
4. Intermediate stage HCC as defined by the following criteria:
* Disease not amenable to curative surgery, liver transplantation or curative ablation BUT disease amenable to TACE at enrollment as judged by the investigator.
* No massive multinodular pattern preventing adequate TACE
* No tumor of a diffuse infiltrative HCC type (hypovascular infiltrative tumors with ill-defined borders)
* Patent portal vein flow
12. Patients with seizure disorder requiring medication.
13. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
14. Evidence or history of bleeding diathesis or any hemorrhage or bleeding event \> CTCAE grade 3 within 4 weeks prior to randomization.
15. Non-healing wound, ulcer, or bone fracture.
16. Renal failure requiring hemo- or peritoneal dialysis.
17. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation including a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein; known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation.
18. Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), with the following exception: patients with a positive HIV test at screening are eligible, provided they are stable on anti-retroviral therapy, have a CD4 count \> 200 cells/µL, and have an undetectable viral load.
19. Active tuberculosis
20. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
21. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan Note: History of radiation pneumonitis within the radiation field (fibrosis) is permitted.
22. Persistent proteinuria of CTCAE Grade 3 or higher (\> 3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).
23. Pregnant or nursing women
24. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
25. Active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
Note: History of autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone, or controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible based on consultation with the sponsor's medical monitor. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
26. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, 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 for the study.
* Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
27. Use of any herbal remedies known to interfere with the liver or other major organ functions. Patients must notify the investigator of all herbal remedies used during the study.
28. Administration of a live, attenuated vaccine within four weeks prior to start of enrollment, or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last TACE procedure.
29. History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Other similar cases can be considered after discussion with lead investigators and sponsor.
30. Receipt of an investigational drug within 28 days prior to initiation of study drug
31. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent or patients with substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
Exclusion Criteria
5. Patients with recurrence after resection/ablation or after previous TACE are eligible, if they - according to the investigator - have an indication for (additional) TACE
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at enrollment.
8. Adequate organ and bone marrow function
9. Life expectancy of ≥ 3 months
10. The following laboratory values obtained less than or equal to 7 days prior to randomization.
* Total bilirubin ≤ 3.0 x the upper limit of normal (ULN)
* Urine dipstick for proteinuria ≤ 2+ (within 7 days prior to randomization) Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours
* The following other laboratory values measured within 7 days prior to randomization are either normal or if abnormal do not represent a medical contraindication for TACE and atezolizumab/bevacizumab as judged by the investigator: Platelet count, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine, INR or aPTT, alkaline phosphatase, neutrophil count (ANC), and serum albumin.
11. Negative serum pregnancy test done lesser than or equal to 7 days prior to randomization, for females of childbearing potential only.
12. No presence of untreated or incompletely treated varices with bleeding or high-risk for bleeding: Availability of esophagogastroduodenoscopy (not older than 6 months) in which all size of varices (small to large) had been assessed and varices were treated per local standard of care prior to randomization.
13. Absence of other severe comorbidities
14. Resolution of any acute, clinically significant treatment-related adverse events from prior therapy/procedure to Grade ≤ 1 prior to randomization, with the exception of alopecia.
15. For patients with active hepatitis B virus (HBV):
* HBV DNA ≤ 2000 IU/mL obtained within 28 days prior to randomization, AND
* Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study.
16. For patients with active hepatitis C virus (HCV):
* Patients positive for hepatitis C virus (HCV) antibody are eligible, also if polymerase chain reaction testing is positive for HCV ribonucleic acid (RNA).
* However, anti-viral therapy against HCV is only allowed prior to trial but not during the trial.
* For HBV and HCV co-infection refer to exclusion criterion # 11.
17. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last TACE procedure.
* A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
* Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
18. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
* With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 6 months after the last dose of bevacizumab or 1 month after the last TACE procedure. Men must refrain from donating sperm during this same period.
* With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of bevacizumab or 1 month after the last TACE procedure to avoid exposing the embryo.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
* There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.
1. 1\. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC (only if proven by biopsy).
2. Previous treatment with atezolizumab or bevacizumab.
3. Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of cancer immunotherapy for HCC.
4. Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control.
• Patients with ascites requiring pharmacologic intervention (e.g. diuretics) and stable for ≥ 2 months on low doses of diuretics (spironolactone 100 mg/d or equivalent) for ascites are eligible. Of note, diuretics for other indications such as congestive heart failure are not considered in this regard.
5. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 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.
6. Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, as well as unstable arrhythmias (note: beta blockers or digoxin are permitted), unstable angina, new-onset angina (begun within the last 3 months).
7. Uncontrolled hypertension defined by a systolic blood pressure (BP) ≥ 150 mmHg or diastolic blood pressure (BP) ≥ 100 mmHg, with or without antihypertensive medication. Prior history of hypertensive crisis or hypertensive encephalopathy. Patients with initial blood pressure (BP) elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria.
8. Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose (prophylactic anticoagulation permitted, e.g. new oral anticoagulants \[apixaban, dabigatran, rivaroxaban\], LMW heparin, ASA up to 300 mg/qd).
9. Arterial or venous thrombotic or embolic events such as cerebro-vascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism ≤6 months prior to randomization.
10. With regards to eligibility for adequate TACE, patients presenting with either of the following conditions are excluded:
* Past history of bilioenteric anastomosis or biliary procedure (e.g., endoscopic papillotomy or biliary stenting) or patients with aerobilia
* Central biliary obstruction (right or left intrahepatic duct, common hepatic duct, common bile duct)
* Celiac occlusion
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at enrollment.
8. Adequate organ and bone marrow function
9. Life expectancy of ≥ 3 months
10. The following laboratory values obtained less than or equal to 7 days prior to randomization.
* Total bilirubin ≤ 3.0 x the upper limit of normal (ULN)
* Urine dipstick for proteinuria ≤ 2+ (within 7 days prior to randomization) Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours
* The following other laboratory values measured within 7 days prior to randomization are either normal or if abnormal do not represent a medical contraindication for TACE and atezolizumab/bevacizumab as judged by the investigator: Platelet count, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine, INR or aPTT, alkaline phosphatase, neutrophil count (ANC), and serum albumin.
11. Negative serum pregnancy test done lesser than or equal to 7 days prior to randomization, for females of childbearing potential only.
12. No presence of untreated or incompletely treated varices with bleeding or high-risk for bleeding: Availability of esophagogastroduodenoscopy (not older than 6 months) in which all size of varices (small to large) had been assessed and varices were treated per local standard of care prior to randomization.
13. Absence of other severe comorbidities
14. Resolution of any acute, clinically significant treatment-related adverse events from prior therapy/procedure to Grade ≤ 1 prior to randomization, with the exception of alopecia.
15. For patients with active hepatitis B virus (HBV):
* HBV DNA ≤ 2000 IU/mL obtained within 28 days prior to randomization, AND
* Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study.
16. For patients with active hepatitis C virus (HCV):
* Patients positive for hepatitis C virus (HCV) antibody are eligible, also if polymerase chain reaction testing is positive for HCV ribonucleic acid (RNA).
* However, anti-viral therapy against HCV is only allowed prior to trial but not during the trial.
* For HBV and HCV co-infection refer to exclusion criterion # 11.
17. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last TACE procedure.
* A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
* Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
18. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
* With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 6 months after the last dose of bevacizumab or 1 month after the last TACE procedure. Men must refrain from donating sperm during this same period.
* With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of bevacizumab or 1 month after the last TACE procedure to avoid exposing the embryo.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
* There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.
1. 1\. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC (only if proven by biopsy).
2. Previous treatment with atezolizumab or bevacizumab.
3. Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of cancer immunotherapy for HCC.
4. Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control.
• Patients with ascites requiring pharmacologic intervention (e.g. diuretics) and stable for ≥ 2 months on low doses of diuretics (spironolactone 100 mg/d or equivalent) for ascites are eligible. Of note, diuretics for other indications such as congestive heart failure are not considered in this regard.
5. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 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.
6. Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, as well as unstable arrhythmias (note: beta blockers or digoxin are permitted), unstable angina, new-onset angina (begun within the last 3 months).
7. Uncontrolled hypertension defined by a systolic blood pressure (BP) ≥ 150 mmHg or diastolic blood pressure (BP) ≥ 100 mmHg, with or without antihypertensive medication. Prior history of hypertensive crisis or hypertensive encephalopathy. Patients with initial blood pressure (BP) elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria.
8. Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose (prophylactic anticoagulation permitted, e.g. new oral anticoagulants \[apixaban, dabigatran, rivaroxaban\], LMW heparin, ASA up to 300 mg/qd).
9. Arterial or venous thrombotic or embolic events such as cerebro-vascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism ≤6 months prior to randomization.
10. With regards to eligibility for adequate TACE, patients presenting with either of the following conditions are excluded:
* Past history of bilioenteric anastomosis or biliary procedure (e.g., endoscopic papillotomy or biliary stenting) or patients with aerobilia
* Central biliary obstruction (right or left intrahepatic duct, common hepatic duct, common bile duct)
* Celiac occlusion
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Salah Eddin Al-Batran, Prof. Dr.
Role: STUDY_DIRECTOR
Institut für Klinische Krebsforschung IKF GmbH, Frankfurt, Germany
Peter Galle, Prof. Dr.
Role: PRINCIPAL_INVESTIGATOR
Universitätsmedizin Mainz, Germany
Jordi Bruix, Prof. Dr.
Role: PRINCIPAL_INVESTIGATOR
Barcelona Clinic Liver Cancer, Universitat de Barcelona, Spain
Locations
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LKH - Univ. Klinikum Graz
Graz, , Austria
Site Status
RECRUITING
Medzinische Universität Innsbruck
Innsbruck, , Austria
Site Status
RECRUITING
Klinikum Klagenfurt am Wörthersee
Klagenfurt, , Austria
Site Status
RECRUITING
Ordensklinikum Linz
Linz, , Austria
Site Status
RECRUITING
Universitätsklinikum St. Pölten
Sankt Pölten, , Austria
Site Status
RECRUITING
Medizinische Universität Wien
Vienna, , Austria
Site Status
RECRUITING
Institut Sainte-Catherine
Avignon, , France
Site Status
RECRUITING
Hôpital Jean-Verdier Avicenne
Bobigny, , France
Site Status
RECRUITING
CHU Bordeaux
Bordeaux, , France
Site Status
RECRUITING
CHU Clermont-Ferrand CHU Estaing
Clermont-Ferrand, , France
Site Status
RECRUITING
Beaujon Hospital
Clichy, , France
Site Status
RECRUITING
CHU Grenoble
Grenoble, , France
Site Status
RECRUITING
Croix-Rousse Hopital
Lyon, , France
Site Status
RECRUITING
Saint Joseph Hopital - Marseille
Marseille, , France
Site Status
RECRUITING
Hôpital Universitaire Pitié Salpêtrière
Paris, , France
Site Status
RECRUITING
Centre Hépato-biliaire Paul Brousse
Villejuif, , France
Site Status
RECRUITING
University Hospital RWTH Aachen
Aachen, , Germany
Site Status
RECRUITING
Klinikum St. Marien Amberg
Amberg, , Germany
Site Status
RECRUITING
Vivantes Klinikum Neukölln
Berlin, , Germany
Site Status
RECRUITING
Universitätsklinikum Bochum
Bochum, , Germany
Site Status
RECRUITING
Uniklinik Köln
Cologne, , Germany
Site Status
RECRUITING
Universitätsklinikum Dresden
Dresden, , Germany
Site Status
RECRUITING
Universitätsklinikum Düsseldorf
Düsseldorf, , Germany
Site Status
RECRUITING
Universitätsklinikum Erlangen
Erlangen, , Germany
Site Status
RECRUITING
Klinikum Esslingen
Esslingen am Neckar, , Germany
Site Status
RECRUITING
Universitätsklinikum Frankfurt
Frankfurt, , Germany
Site Status
RECRUITING
Krankenhaus Nordwest
Frankfurt am Main, , Germany
Site Status
RECRUITING
Universitätsklinikum Freiburg
Freiburg im Breisgau, , Germany
Site Status
RECRUITING
Universitätsmedizin Göttingen
Göttingen, , Germany
Site Status
RECRUITING
Medizinische Hochschule Hannover
Hanover, , Germany
Site Status
RECRUITING
Klinikum Konstanz
Konstanz, , Germany
Site Status
RECRUITING
Krankenhaus Maria-Hilf Krefeld
Krefeld, , Germany
Site Status
RECRUITING
Universitätsklinikum Schleswig-Holstein
Lübeck, , Germany
Site Status
RECRUITING
Universitätsmedizin Mainz
Mainz, , Germany
Site Status
RECRUITING
Universitätsklinikum Mannheim
Mannheim, , Germany
Site Status
RECRUITING
Universitätsklinikum Marburg
Marburg, , Germany
Site Status
RECRUITING
Klinikum rechts der Isar München
München, , Germany
Site Status
RECRUITING
Klinikum Mutterhaus Trier
Trier, , Germany
Site Status
RECRUITING
Krankenhaus der Barmherzigen Brüder Trier
Trier, , Germany
Site Status
RECRUITING
Uniklinik Ulm
Ulm, , Germany
Site Status
RECRUITING
St. Josefs Hospital Wiesbaden
Wiesbaden, , Germany
Site Status
RECRUITING
Universitätsklinikum Würzburg
Würzburg, , Germany
Site Status
RECRUITING
Policlinico S. Orsola Bologna
Bologna, , Italy
Site Status
RECRUITING
Instituto Tumori della Romagna IRST IRCCS
Meldola, , Italy
Site Status
RECRUITING
Policlinico di Milano
Milan, , Italy
Site Status
RECRUITING
Instituto di Tumori
Milan, , Italy
Site Status
RECRUITING
Università di Pisa (UNIPI)
Pisa, , Italy
Site Status
RECRUITING
AOUI Verona
Verona, , Italy
Site Status
RECRUITING
Hokkaido University Hospital
Hokkaido, , Japan
Site Status
RECRUITING
Kobe University Hospital
Kobe, , Japan
Site Status
RECRUITING
Kumamoto University Hospital
Kumamoto, , Japan
Site Status
RECRUITING
University Hospital Kyoto Prefectural University of Medicine
Kyoto, , Japan
Site Status
RECRUITING
Nagasaki University Hospital
Nagasaki, , Japan
Site Status
RECRUITING
Kindai University Hospital
Osaka, , Japan
Site Status
RECRUITING
Saitama Medical University Hospital
Saitama, , Japan
Site Status
RECRUITING
Fujita Health University Hospital
Toyoake, , Japan
Site Status
RECRUITING
Yamaguchi University Hospital
Ube, , Japan
Site Status
RECRUITING
Hospital Universitario de Alicante
Alicante, , Spain
Site Status
RECRUITING
Hospital Infanta Cristina
Badajoz, , Spain
Site Status
RECRUITING
Hospital Germans Trias I Pujol
Badalona, , Spain
Site Status
RECRUITING
Hospital Universitari Vall d'Hebrón
Barcelona, , Spain
Site Status
RECRUITING
Barcelona Clinic Liver Cancer, Universitat de Bracelona
Barcelona, , Spain
Site Status
RECRUITING
Hospital Puerta del Mar
Cadiz, , Spain
Site Status
RECRUITING
Hospital de Jaen
Jaén, , Spain
Site Status
RECRUITING
Hospital Universitario Gregorio Marañon
Madrid, , Spain
Site Status
RECRUITING
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Site Status
RECRUITING
Hospital Fundación Jimenez Diaz
Madrid, , Spain
Site Status
RECRUITING
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, , Spain
Site Status
RECRUITING
Hospital de Alcorcón
Madrid, , Spain
Site Status
RECRUITING
Hospital de Málaga
Málaga, , Spain
Site Status
RECRUITING
Hospital Marqués de Valdecilla
Santander, , Spain
Site Status
RECRUITING
Hospital Universitario Virgen del Rocío
Seville, , Spain
Site Status
RECRUITING
Countries
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Austria
France
Germany
Italy
Japan
Spain
Central Contacts
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Facility Contacts
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Other Identifiers
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2020-004210-35
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2024-512953-26-00
Identifier Type: CTIS
Identifier Source: secondary_id
ABC-HCC
Identifier Type: -
Identifier Source: org_study_id
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