Hepatocellular Carcinoma
Conditions
Keywords
hepatocellular carcinoma, HCC, intermediate stage, atezolizumab, bevacizumab, TACE
Brief summary
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.
Detailed description
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.
Interventions
DRUGAtezolizumab
1200 mg atezolizumab intravenously Q3W (max 32 cycles, up to 24 months)
DRUGBevacizumab
15 mg/kg intravenously Q3W (max 32 cycles, up to 24 months)
PROCEDURETACE
Locoregional therapy will be performed as a standard-of-care procedure
Sponsors
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * No main portal vein invasion/thrombosis on baseline/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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to failure of treatment strategy | 48 months - assessed every 8 weeks (±7days) | The primary endpoint is defined as the time from randomization until death or need for a further therapeutic option, defined for each arm as follows: * Arm A: Time from randomization until the failure of strategy does not allow for further treatment with atezolizumab + bevacizumab; or death, whichever comes first. * Arm B: Time from randomization until the failure of strategy does not allow for further TACE therapy; or death, whichever comes first. Failure of strategy (in brief): failure of strategy is reached in case of progressive disease accompanied by any of the following: loss of clinical benefit, unacceptable toxicity, liver function deterioration, therapy not further applicable for other reasons. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 48 months | Time from the date of randomization until the date of death due to any cause. A subject who has not died will be censored at last known date alive. |
| Overall Survival Rate at 24 months (OS@24) | 24 months | The proportion of patients assigned to a treatment arm known to be alive at 24 months after randomization. |
| Objective Response Rate (ORR) | 48 months | The proportion of patients assigned to a treatment arm with a confirmed best response of Complete Response (CR) or Partial Response (PR). Response will be assessed according to HCC mRECIST. |
| Time to Progression (TTP) | 48 months | Time from the date of randomization until the date of first objective disease progression. Subjects who have not progressed will be censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. Subjects who die without experiencing a progress first will be censored on their date of death. |
| Time to loss of systemic treatment options (TTSYS) | 24 months | Time from the date of randomization until the date the patient reaches a state of being unfit for any subsequent systemic treatment option (BSC as only option left) or the date of death whichever occurs first. Subjects who end systemic treatment at their own request will be censored at the day of end of systemic treatment. Subjects who are lost to follow-up will be censored at the date last known to be systemically treated. |
| Progression free survival (PFS) | 48 months | Time from the date of randomization until the date of first objective disease progression or death. Subjects who did not progress or die will be censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. |
| Treatment-related and -unrelated toxicities (AEs, SAEs) according to NCI CTCAE v5.0 | 48 months | Summary of adverse events by treatment arm and CTCAE (version 5.0) grade and frequency of clinically significant abnormal laboratory parameters. |
| QoL (EORTC QLQ-C30 and HCC18 sub-questionnaire) | 48 months | QoL mean values and response as well as time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment. |
| Duration of Treatment | 24 months | From start of treatment to permanent discontinuation of the treatment arms A and B. |
| Duration of Response (DOR) | 48 months | Time from initial response to progressive disease or death in patients in treatment arms A and B with a confirmed best response of Complete Response (CR) or Partial Response (PR) according to HCC mRECIST. Subjects who did not progress or die will be censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. |
| Time to deterioration of liver function | 48 months | Time from the date of randomization until liver function deterioration is registered according to definition given for failure of strategy. Only patients experiencing a deterioration of liver function are included into this analysis |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory endpoint - Correlation of biomarkers for study endpoints | 48 months | Tissue, blood and stool samples will be collected to identify prognostic and predictive angiogenic and immune related biomarkers (tissue and circulating) for study endpoints. |
| Exploratory endpoint - PD-L1 expression | 48 months | PD-L1 expression will be analyzed by immunohistochemistry on available FFPE tissue samples |
Countries
Austria, France, Germany, Italy, Japan, Spain
Contacts
Primary ContactPeter Galle, Prof. Dr.
Backup ContactJohanna Riedel, Dr.
Outcome results
None listed