CTRI/2024/11/077188尚未招募3 期
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
Frankfurter Institut für Klinische Krebsforschung IKF GmbH1 个研究点 分布在 1 个国家目标入组 434 人开始时间: 2024年12月10日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 434
- 试验地点
- 1
- 主要终点
- The main purpose of this phase IIIb study is to test the efficacy and safety of atezolizumab in combination
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients must meet all of the following criteria to be eligible for the study
- •Signed Informed Consent Form available
- •Patients more than or equal to 18 years of age at time of signing Informed Consent Form
- •Confirmed hepatocellular carcinoma diagnosis based on histopathological findings from tumor tissue or typical diagnostic imaging on dynamic CT or MRI according to AASLD criteria.
- •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.
- •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
- •Child-Pugh score class A or B7 without ascites requiring more than 100 mg of spironolactone or day at enrollment.
- •Eastern Cooperative Oncology Group ECOG performance status of 0 to 1 at enrollment.
- •Adequate organ and bone marrow function
- •Life expectancy of more than or equal to 3 months
- •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.
- •Negative serum pregnancy test done lesser than or equal to 7 days prior to randomization, for females of childbearing potential only.
- •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.
- •Absence of other severe comorbidities
- •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.
- •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.
- •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
- •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.
- •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.
排除标准
- •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.
结局指标
主要结局
The main purpose of this phase IIIb study is to test the efficacy and safety of atezolizumab in combination
时间窗: assessed every 8 weeks (±7days)
with bevacizumab compared to TACE in patients with intermediate stage liver cancer.
时间窗: assessed every 8 weeks (±7days)
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.
时间窗: assessed every 8 weeks (±7days)
次要结局
- 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)
研究者
Dr Vikas Ostwal
Tata Memorial Centre
研究点 (1)
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