Study Evaluating the Benefit of Adding Ipilimumab to the Combination of Atezolizumab and Bevacizumab in Patients With Hepatocellular Carcinoma Receiving First-line Systemic Therapy
TRIPLET
Randomised, Open-label, Phase II-III Study Evaluating the Benefit of Adding Ipilimumab to the Combination of Atezolizumab and Bevacizumab in Patients With Hepatocellular Carcinoma Receiving First-line Systemic Therapy
2 other identifiers
interventional
229
1 country
45
Brief Summary
TRIPLET HCC is a phase II-III trial that assess the effectivness of addition of ipilimumab to the combination atezolizumab-bevacizumab, on global survival and response to the treatment, for patients with advanced or metastatic hepatocellular carcinoma. The theoretical duration of the study is 5 years. In the scope of this study, each patient will have 2 years of treatment and 2 years of follow-up from their enrollment date.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2023
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 16, 2022
CompletedFirst Posted
Study publicly available on registry
December 27, 2022
CompletedStudy Start
First participant enrolled
March 9, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 12, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 12, 2025
CompletedMarch 9, 2026
September 1, 2024
2.2 years
December 16, 2022
March 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Objective response of treatment (Phase II)
Assess the percentage of patients with an objective response (complete response or partial response) according to the investigator (RECIST v1.1) for both treatments arms,
24 months after beginning of treatment
Overall survival (Phase III)
The overall survival is defined as the time to death (whatever the cause) or date of last news
From randomization until death or last news for alive patients, up to 2 years
Secondary Outcomes (2)
Progression-free survival (PFS)
From randomization until progression, death or last news for alive patients, up to 2 years
Objective response rate (OR) under treatment (Phase III)
24 months after beginning of treatment
Study Arms (2)
DOULET ATEZOLIZUMAB-BEVACIZUMAB
ACTIVE COMPARATORStandard treatment of HCC by the combination atezolizumab-bevacizumab, 1 cure each 3 weeks during 24 months
TRIPLET ATEZOLIZUMAB BEVACIZUMAB IPILIMUMAB
EXPERIMENTALStandard treatment of HCC by the combination atezolizumab-bevacizumab with addition of ipilimumab for the 4 firsts cures of treatment each 3 weeks, then only treatment by the doublet atezolizumab-bevacizumab each 3 weeks. The total duration of treatment is 24 months.
Interventions
One of the standard treatment's product for HCC management
Administration of a combine treatment by atezolizumab and bevacizumab, with addition of ipilimumab for patients enrolled in the experimental arm
One of the standard treatment's product for HCC management
Eligibility Criteria
You may qualify if:
- Age ≥ 18 years
- Histologically proven hepatocellular carcinoma (HCC) on biopsy less than two years old. If no histological evidence, a tumour (mandatory) and non-tumour (optional) liver biopsy is required.
- WHO 0 or 1
- HCC not amenable to curative treatment by surgery, thermo-ablation or liver transplantation, or to intra-arterial palliative treatment (IAP) for intermediate BCLC-B HCC.
- Advanced (BCLC-C) or intermediate (BCLC-B) HCC after failure or contraindication of the CEL
- Normal Troponin-T
- Patients with controlled cardiovascular disease for at least 6 months
- No clinically evident ascites, no history of clinical ascites, or encephalopathy due to liver failure
- Adequate liver function: AST and ALT ≤ 5 x ULN (upper normal limit), total bilirubin ≤ 35 µM/L, albumin ≥ 28 g/L and Child-Pugh A score (if associated cirrhosis)
- Hematological (hemoglobin \> 8.5 g/dL, platelets \> 60 G/L, PNN \> 1.5 G/L) and renal function (creatinine clearance ≥ 40ml/min according to the appropriate MDRD formula)
- At least one target lesion measurable according to RECIST v1.1 criteria
- Oesophageal endoscopy less than 6 months old. All patients with varicose veins of any grade should be treated with β-blockers prior to initiation of therapy, in the absence of contraindications.
- Women of childbearing potential must agree to use contraception during the trial treatment and for at least 6 months after discontinuation of the experimental treatments. Men who have sex with women of childbearing potential must agree to use contraception during treatment and for at least 6 months after discontinuation of the experimental treatments
- Ability of the patient to understand, sign and date the informed consent form before randomisation
- Patient affiliated to a social security scheme
You may not qualify if:
- Patients who have already received systemic therapy for HCC
- Bleeding related to portal hypertension in the last 6 months
- History of abdominal or oesophageal fistula, gastrointestinal perforation or intra-abdominal abscess, diverticulitis or colitis within 6 months prior to randomisation
- Patients on double anti-platelet aggregation therapy
- Patients on chronic non-steroidal anti-inflammatory drugs (except aspirin).
- History of intra-abdominal inflammatory process within 6 months prior to initiation of treatment - including but not limited to - active peptic ulcer, diverticulitis or colitis
- Major surgery or significant traumatic injury within 28 days prior to treatment, abdominal surgery or significant abdominal traumatic injury within 60 days prior to treatment, or the need for major surgery during the therapeutic trial
- Hypersensitivity to any of the study drugs or their excipients
- Allergy to one of the components of Chinese hamster ovary cells.
- Other malignant tumours within the last 2 years, except for carcinoma in situ of the uterus or basal cell or squamous cell skin carcinoma or any other carcinoma in situ, considered curedHistory of severe active life-threatening autoimmune disease
- Interstitial lung disease
- Chronic HBV infection with HBV DNA \> 500 IU/ml, infected patients, cirrhotic or not, should be treated with nucleotide/nucleoside analogues.
- Known HIV infection
- Immunosuppression, including subjects with conditions requiring systemic corticosteroid treatment (\>10 mg/day prednisone equivalent)
- History of organ transplantation
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (45)
Chu Amiens Picardie
Amiens, France
CHU
Angers, France
Privé LES BONNETTES
Arras, France
Chu Avicienne
Bobigny, France
Privé Bordeaux Nord
Bordeaux, France
Ch Duchenne
Boulogne-sur-Mer, France
Chu Morvan
Brest, France
Centre Hospitalier
Cholet, France
Chu Estaing
Clermont-Ferrand, France
Chu Beaujon
Clichy, France
CH HCC
Colmar, France
Chu Francois Mitterand
Dijon, France
CHD Vendée
La Roche-sur-Yon, France
Chu Dupuytren
Limoges, France
Chu La Croix Rousse
Lyon, France
CAC Paoli Calmettes
Marseille, France
Chu La Timone
Marseille, France
Privé Saint-Joseph
Marseille, France
Chu Saint-Eloi
Montpellier, France
CHU Hôtel Dieu
Nantes, France
Privé CONFLUENT
Nantes, France
Chu L'Archet
Nice, France
Chu La Pitie Salpetriere
Paris, France
Chu Saint Antoine
Paris, France
Privé Saint-Joseph
Paris, France
Centre Hospitalier
Pau, France
CH Saint-Jean
Perpignan, France
Chu Haut Leveque
Pessac, France
Chu Haut-Leveque
Pessac, France
Privé HPCA
Plérin, France
Chu La Miletrie
Poitiers, France
Ch Annecy Genevois
Pringy, France
Centre Hospitalier
Quimper, France
CHU Robert Debré
Reims, France
CAC Eugène Marquis
Rennes, France
Chu Charles Nicolle
Rouen, France
Chu Saint-Etienne
Saint-Priest-en-Jarez, France
Centre Hospitalier
St-Malo, France
Cac Icans
Strasbourg, France
Privé Sainte Anne
Strasbourg, France
Chu Rangueil
Toulouse, France
CHRU Hôpitaux de Tours
Tours, France
Centre Hospitalier
Valence, France
Chu Brabois
Vandœuvre-lès-Nancy, France
CAC Gustave Roussy
Villejuif, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 16, 2022
First Posted
December 27, 2022
Study Start
March 9, 2023
Primary Completion
May 12, 2025
Study Completion
May 12, 2025
Last Updated
March 9, 2026
Record last verified: 2024-09