2022-501217-31-00招募中3 期
PRODIGE 81-FFCD 2101-TRIPLET: Randomized, 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
Fondation Franc.Cancerologie Digestive, Fondation Franc.Cancerologie Digestive59 个研究点 分布在 1 个国家目标入组 574 人开始时间: 2022年10月27日最近更新:
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 574
- 试验地点
- 59
- 主要终点
- Phase II : objective response (complete response or partial response)within the first 24 weeks (9 cycles) for both arms treatment
研究概览
简要总结
Phase II: To assess the percentage of patients with an objective response (complete response or partial response) according to the investigator (RECIST v1.1) within the first 24 weeks (9 cycles) for both treatment arms, in patients with hepatocellular carcinoma.
Phase III: to compare the overall survival between the triplet and doublet arms.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years
- •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
- •Histologically proven hepatocellular carcinoma (HCC) on biopsy less than two years old. If not histologically proven, it is necessary to perform a tumour (mandatory) and non-tumour (optional) liver biopsy.
- •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.
- •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.
- •Advanced (BCLC-C) or intermediate (BCLC-B) HCC after failure or contraindication of the CEL
- •Normal Troponin-T
- •No clinically evident ascites or history of clinical ascites, liver failure encephalopathy
- •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 cirrhosis associated).
- •Adequate haematological and renal function (haemoglobin > 8.5 g/dl, platelets > 60 G/L, PNN > 1.5 G/L) and renal function (creatinine clearance ≥ 40ml/min according to MDRD formula)
- •Patients with controlled cardiovascular disease for at least 6 months
- •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.
排除标准
- •Patients who have already received systemic therapy for HCC
- •Medically uncontrolled hypertension (≥ 150 mm Hg and/or diastolic blood pressure superior to 90 mm Hg)
- •History of arterial aneurysm at high risk of bleeding
- •Bleeding related to portal hypertension in the last 6 months
- •Alive attenuated vaccine within 28 days prior to randomisation
- •Pregnant or breastfeeding women.
- •Person under guardianship, or person deprived of liberty.
- •Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons
- •History of abdominal or oesophageal fistula, gastrointestinal perforation or intra-abdominal abscess, diverticulitis or colitis within 6 months prior to randomisation
- •Patients on dual anti-platelet therapy
- •Patients on chronic non-steroidal anti-inflammatory drugs (except aspirin)
- •History of severe active life-threatening autoimmune disease
- •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 any component of Chinese hamster ovary cells. Other malignancies 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 cured
- •History of pericardial abnormalities possibly immune-related (pericarditis or cardiac tamponade)
- •Patient who has received immunotherapy (including anti-CTLA-4, anti-PD-1 or anti-PD-L1 agents) or anti-VEGF antibody therapy
- •Patients who has previously received external radiotherapy up to 1 month before the start of the study treatment, or 3 months beofre the start of the study treatment in case of radio embolization
- •Central nervous system metastases
- •Active bacterial infection
- •Patients with uncontrolled cardiovascular disease
- •Interstitial lung disease
- •History of arterial thromboembolic events, including stroke, transient ischemic attack and myocardial infarction, if less than 6 months old and unresolved
- •History of venous thromboembolic disease, if less than 6 months old
- •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
- •Non-healing decaying wound, active ulcer or untreated bone fracture
- •Proteinuria ≥ 2+ on urine dipstick if confirmation of 24h proteinuria showing a level ≥ 2 g/24 hours
结局指标
主要结局
Phase II : objective response (complete response or partial response)within the first 24 weeks (9 cycles) for both arms treatment
Phase II : objective response (complete response or partial response)within the first 24 weeks (9 cycles) for both arms treatment
Phase III : overall survival between the two arms
Phase III : overall survival between the two arms
次要结局
- Radiation progression-free survival (PFS)
- Objective response rate (OR) under treatment
- Rate of disease control (complete response or partial response or stability)
- Response time
- Median time to progression
- Median time to WHO degradation>2
- Time to objective response
- Tolerance (NCI CTC v4.0 assessed treatment and non-treatment related adverse events (bevacizumab and immunotherapy)
- Rate of permanent discontinuation of protocol treatment due to a study treatment-related effect.
- Quality of life according to the EORTC QLQ-C30 and its HCC supplement EORTC QLQ-HCC18, time to deterioration of the quality of life score.
- Overall survival (median) - Phase II patients
研究者
national coordinator
Scientific
Fondation Franc.Cancerologie Digestive
研究点 (59)
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