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CTRI Number  CTRI/2024/11/077188 [Registered on: 21/11/2024] Trial Registered Prospectively
Last Modified On: 24/07/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   A Phase IIIb, randomized, multicenter, open-label trial of evaluating safety and efficacy with treatment of Atezolizumab and Bevacizumab as a novel alternative treatment method to TACE in intermediate stage liver cancer patients. 
Scientific Title of Study   The ABC-HCC Trial:A Phase IIIb, randomized, multicenter, open-label trial of Atezolizumab plus Bevacizumab versus transarterial Chemoembolization (TACE) in intermediate-stage HepatoCellular Carcinoma  
Trial Acronym  The ABC-HCC Trial 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Vikas Ostwal 
Designation  Professor and consultant Medical Oncologist 
Affiliation  Tata Memorial Centre 
Address  Room number 1102,Department of Medical Oncology GI, 11th Floor, Homi Bhabha Block, Tata Memorial Hospital, Dr. E. Borges road, Parel, Mumbai MAHARASHTRA 400012 India

Mumbai
MAHARASHTRA
400012
India 
Phone  9702288801  
Fax    
Email  dr.vikas.ostwal@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Vikas Ostwal 
Designation  Professor and consultant Medical Oncologist 
Affiliation  Tata Memorial Centre 
Address  Room number 1102,Department of Medical Oncology GI, 11th Floor, Homi Bhabha Block, Tata Memorial Hospital, Dr. E. Borges road, Parel, Mumbai MAHARASHTRA 400012 India

Mumbai
MAHARASHTRA
400012
India 
Phone  9702288801  
Fax    
Email  dr.vikas.ostwal@gmail.com  
 
Details of Contact Person
Public Query  
Name  Dr Vikas Ostwal 
Designation  Professor and consultant Medical Oncologist 
Affiliation  Tata Memorial Centre 
Address  Room number 1102,Department of Medical Oncology GI, 11th Floor, Homi Bhabha Block, Tata Memorial Hospital, Dr. E. Borges road, Parel, Mumbai MAHARASHTRA 400012 India

Mumbai
MAHARASHTRA
400012
India 
Phone  9702288801  
Fax    
Email  dr.vikas.ostwal@gmail.com  
 
Source of Monetary or Material Support  
The study will be conducted in Tata Memorial Hospital Mumbai India. The detailed address is Tata Memorial Hospital, Dr Ernest Borges Road, Parel, Mumbai 400012, Maharashtra, India  
 
Primary Sponsor  
Name  Frankfurter Institut für Klinische Krebsforschung IKF GmbH 
Address  Institut für Klinische Krebsforschung IKF GmbH, Steinbacher Hohl 2-26/Haus B, 2. OG, 60488 Frankfurt am Main, Germany 
Type of Sponsor  Research institution 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India
Germany
Spain  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Vikas Ostwal   Tata Memorial Hospital  OPD 319, Dept of GI Medical Oncology, 3rd floor, Homi Bhabha Building, Tata Memorial Hospital, Dr Ernest Borges Road, Parel, Mumbai 400012 MAHARASHTRA, India
Mumbai
MAHARASHTRA 		 9702288801

dr.vikas.ostwal@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
Mahamana Pandit Madan Mohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital  Approved 
Tata Memorial Hospital Institutional Ethics Committee-I  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C220||Liver cell carcinoma,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Inj Atezolizumab plus Inj bevacizumab  Patients will receive the following treatment regimen in the study Arm A experimental arm-atezolizumab + bevacizumab Atezolizumab 1200 mg IV infusion on Day 1 plus Bevacizumab 15 mg per kg IV infusion on Day 1 dosed every three weeks that is cycle length 21 days and start of next cycle on day 22 Infusion rate for atezolizumab will be Over 60(± 15)minutes (for the first infusion) 30 (± 10) minutes for subsequent infusions if tolerated. Infusion rate for bevacizumab will be Over 90 (± 15) minutes (for the first infusion) shortening to 60 (± 10) then 30 (± 10) minutes for subsequent infusions if tolerated. Patients should receive their first dose of study drug as soon as possible but not later than 10 working days after randomization. Atezolizumab will be administered first followed by bevacizumab with a minimum of 5 minutes between dosing 
Comparator Agent  TACE - Transarterial Chemoembolization  Transarterial Chemoembolization (using conventional TACE [cTACE] or drug-eluting bead TACE [DEB-TACE]) Patients should be subject to TACE treatment as soon as possible after randomization, but no later than 10 working days after randomization. Sites are responsible to schedule TACE properly to be able to adhere to this provision (deviations from this time window are allowed in very exceptional cases only and only after prior approval by the Lead Coordinating Investigators). 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 to reach, to improve or maintain an objective response (timing according to investigator’s decision) but patients will continue to be scanned for progression by CT or MRI at fixed intervals as described in the Schedule of Assessments. Both conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) approaches are accepted. However, consistency in the TACE procedure and the use of the chemotherapeutic agent has to be maintained for each individual patient. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  Patients must meet all of the following criteria to be eligible for the study
1. Signed Informed Consent Form available
2. Patients more than or equal to 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
No main portal vein invasion/thrombosis on baseline or eligibility imaging. Patients with minimal invasion, (Vp1 and Vp2) may be eligible if no exclusion criteria are violated.
No extrahepatic disease
Note - Patients with HCC beyond Milan criteria who enter a downstaging protocol may be recruited into the trial if they do not present any exclusion criteria.
5. Patients with recurrence after resection or ablation or after previous TACE (are eligible, if they according to the investigator have an indication for (additional) TACE
6. Child-Pugh score class A or B7 without ascites requiring more than 100 mg of spironolactone or day at enrollment.
7. Eastern Cooperative Oncology Group ECOG performance status of 0 to 1 at enrollment.
8. Adequate organ and bone marrow function
9. Life expectancy of more than or equal to 3 months
10. The following laboratory values obtained less than or equal to 7 days prior to randomization.
Total bilirubin less than or equal to 3.0 x the upper limit of normal ULN Urine dipstick for proteinuria less than 2plus within 7 days prior to randomization
Patients discovered to have more than or equal to 2plus proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate less than1 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 or 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 or procedure to Grade less than or equal to 1 prior to randomization, with the exception of alopecia.
15. For patients with active hepatitis B virus HBV HBV DNA less than or equal to 2000 IU or 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 17.
17. For women of childbearing potential: agreement to remain abstinent refrain from heterosexual intercourse or use contraceptive methods with a failure rate of less than 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 more than or equal to12 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 less than 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormonereleasing 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 less than 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. 
 
ExclusionCriteria 
Details  1.Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
2.Prior treatment with atezolizumab or bevacizumab
3.Previous immunotherapy including PD1, PDL1, or CTLA4 inhibitors for HCC
4.Clinically significant ascites requiring nonpharmacologic intervention
5.Recent major surgery or significant trauma within 28 days
6.Significant cardiovascular disease or recent cardiac events
7.Uncontrolled hypertension with systolic greater than or equal to 150 mmHg or diastolic greater than or equal to 100 mmHg
8.Recent use of full dose anticoagulants or thrombolytic agents
9.Arterial or venous thrombotic or embolic events within 6 months
10.Excluded if past biliary procedures or central biliary obstruction
11.Ongoing infection greater than grade 2 as per NCICCTAE version 5.0
12.Seizure disorder requiring medication
13.Prior allogeneic bone marrow or solid organ transplantation
14.Bleeding diathesis or hemorrhage greater than CTCAE grade 3 within 4 weeks
15.Non-healing wounds, ulcers, or bone fractures
16.Renal failure requiring dialysis
17.Hypersensitivity to study drugs or their components
18.HIV or AIDS unless stable on therapy with a CD4 count greater than 200 cells per microliter and undetectable viral load
19.Active tuberculosis
20.Interstitial lung disease or ongoing signs or symptoms
21.History of pulmonary fibrosis, pneumonitis, or active pneumonitis
22.Persistent proteinuria greater than 3.5 grams per 24 hours
23.Pregnant or nursing women
24.Severe concurrent disease or systemic illness
25.Active or history of autoimmune disease with some exceptions
26.Recent systemic immunosuppressive treatment with some exceptions
27.Use of herbal remedies affecting liver or major organ function
28.Recent live attenuated vaccine within four weeks
29.History of malignancy other than HCC within 3 years with some exceptions
30.Recent investigational drug use within 28 days
31.History of non-compliance, substance abuse, or conditions affecting participation









 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
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 endpoint is to evaluate Time to failure of treatment strategy (TTFS [assessed every 8 weeks (±7days)]) defined as the time from randomization until death or need for a further therapeutic option. 		 assessed every 8 weeks (±7days) 
 
Secondary Outcome  
Outcome  TimePoints 
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.
Safety objectives
To evaluate the safety and tolerability of each therapeutic strategy and their respective impact on Quality of
Life.
Biomarker objectives
To identify prognostic and predictive angiogenic and immune related biomarkers (tissue and circulating) for
study endpoints.
To evaluate Overall survival,Overall Survival Rate at 24 months, Objective Response Rate, Time to Progression, Time to loss of systemic treatment options,Progression free survival, Duration of Response, Time to deterioration of liver function, Safety and Quality of Life (QoL) endpoints, to analyse target gene expression and immune cell composition by molecular quantitation of select markers and correlated with clinical efficacy. 		 Overall Survival Rate at 24 months 
 
Target Sample Size   Total Sample Size="434"
Sample Size from India="80" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   10/12/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  22/10/2021 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="6"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   For patients with liver cell cancer at a certain inoperable stage (intermediate BCLC-B stage) the so called standard of care treatment is currently a procedure called transarterial chemoembolization (TACE).  TACE treatment does not serve to cure the cancer, but it is intended to control the spread of the tumor foci. However, due to its invasive nature and its potential to harm liver function, the development of a non-invasive approach to replace TACE is necessary. In the meantime, systemic treatment using combination of Atezolizumab with Bevacizumab is approved for the treatment of advanced liver cell cancer (advanced BCLC-C stage). The antibody Atezolizumab can influence the immune system. The second antibody, Bevacizumab, inhibits the formation of new blood vessels. The ABC-HCC trial wants to evaluate the systemic treatment with Atezolizumab and Bevacizumab as a novel alternative treatment method to TACE to assess the efficacy and safety for the above type of liver cancer patients. 
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