Randomized Controlled Phase II Trial Comparing Trans-Arterial Chemo-Embolization (TACE) With TACE Plus Stereotactic Ablative Radiotherapy (SABR) in Stage BCLC B Hepatocarcinoma (HepSTAR)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Objective response rate at 6 months
研究概览
简要总结
This will be multicentre a phase II randomized controlled and open-label trial. It will compare the 6-months objective response (CR+PR) rates obtained with Drug Eluting Bead Trans-Arterial Chemo-Embolization (DEB-TACE) alone versus DEB-TACE followed by Stereotactic Ablative Radiotherapy (SABR) in patients with hepatocarcinoma stage BCLC B.
This trial will also include one substudy. This substudy will confront the immuno-histochemical results collected on tumoral biopsies to the biological and imaging (MRI) results. Every patient participating to the trial can also participate to this substudy.
详细描述
The patients will be randomized in 2 arms determining the treatment they will receive:
Arm A: actual standard treatment = TACE Arm B: experimental arm = TACE + SABR
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hepatocellular carcinoma larger than 3 cm and non-resectable, with a diagnosis established either by:
- •dynamic imaging (non-invasively), showing a typical contrast enhancement and wash-out
- •histopathology
- •satellite lesions are allowed (at most three lesions) as long as the doses constraints are still achievable
- •Hepatocellular carcinoma belonging to Barcelona Clinic Liver Cancer Stage System class B
- •Tumor must be measurable on a multi-phase MRI according to mRECIST criteria
- •Non-tumoral liver volume ≥ 800 cc
- •Child-Pugh (CP) A to B7 cirrhosis
- •HCC Patients can be included if they require treatment prior to liver transplantation
- •ECOG performance status 0-1
- •AST/ALT < 5 times ULN
- •Initial platelets ≥ 50 000 x 10E9/l, neutrophils > 1500 x 10E9/l, Hb > 9 g/dl
- •Serum creatinine < 1.5 X normal, or calculated Creatinine clearance rate ≥ 60 mL/min
- •As tumor biopsy can be performed after inclusion, pure hepatocellular carcinoma but also mixed hepatocellular carcinoma will be allowed in this trial. Cholangiocarcinoma cannot be included.
- •Written informed consent form to be signed,
- •Patient willing and able to comply to the follow-up schedule
- •Patients in fertile age should use a contraceptive method during treatment and 4 months after.
排除标准
- •Eligibility for resection or ablative treatments
- •Extra hepatic spread of the disease
- •Previous treatment of the same lesion with TACE
- •Previous treatment with selective internal radiotherapy or radiotherapy to the upper abdomen
- •Uncontrolled Ascites
- •Uncontrolled Encephalopathy
- •Any clinical sign of acute viral or non-viral hepatitis (new serological testing are not required)
- •Known current pregnancy
- •Uncontrolled active co-morbidity
研究组 & 干预措施
Trans-Arterial Chemo-embolization (TACE)
Trans-arterial Embolisation will be performed with drug-eluting beads loaded with Doxorubicin. First session will be given within 4 weeks after randomization.
4-phase MRI will be performed every 2 months to assess the response. In case of insufficient response according to the MRI performed at 2 or 4 months, a second or third session of DEB-TACE will be allowed, according to the physician's choice.
Once complete response is achieved, the follow-up period will start. The date of the last session of TACE corresponds to the treatment completion date.
干预措施: Trans-arterial Chemo-Embolization (Procedure)
Trans-Arterial Chemo-embolization (TACE)
Trans-arterial Embolisation will be performed with drug-eluting beads loaded with Doxorubicin. First session will be given within 4 weeks after randomization.
4-phase MRI will be performed every 2 months to assess the response. In case of insufficient response according to the MRI performed at 2 or 4 months, a second or third session of DEB-TACE will be allowed, according to the physician's choice.
Once complete response is achieved, the follow-up period will start. The date of the last session of TACE corresponds to the treatment completion date.
干预措施: Doxorubicin (Drug)
TACE+Stereotactic Ablative Radiotherapy
The first part of the treatment, which is the DEB-TACE delivery, will be exactly the same than in arm A. The radiotherapy (SABR) will then start within 4 to 6 weeks after.
Afterwards, 4-phase MRI will be performed every 2 months to assess the response. In case of insufficient response according to the MRI performed at 2 or 4 months, a second or third session of DEB-TACE will be allowed, according to the physician's choice.
Once complete response is achieved, the follow-up period will start. The date of the last SABR fraction or the last session of TACE corresponds to the treatment completion date.
干预措施: Trans-arterial Chemo-Embolization (Procedure)
TACE+Stereotactic Ablative Radiotherapy
The first part of the treatment, which is the DEB-TACE delivery, will be exactly the same than in arm A. The radiotherapy (SABR) will then start within 4 to 6 weeks after.
Afterwards, 4-phase MRI will be performed every 2 months to assess the response. In case of insufficient response according to the MRI performed at 2 or 4 months, a second or third session of DEB-TACE will be allowed, according to the physician's choice.
Once complete response is achieved, the follow-up period will start. The date of the last SABR fraction or the last session of TACE corresponds to the treatment completion date.
干预措施: Doxorubicin (Drug)
TACE+Stereotactic Ablative Radiotherapy
The first part of the treatment, which is the DEB-TACE delivery, will be exactly the same than in arm A. The radiotherapy (SABR) will then start within 4 to 6 weeks after.
Afterwards, 4-phase MRI will be performed every 2 months to assess the response. In case of insufficient response according to the MRI performed at 2 or 4 months, a second or third session of DEB-TACE will be allowed, according to the physician's choice.
Once complete response is achieved, the follow-up period will start. The date of the last SABR fraction or the last session of TACE corresponds to the treatment completion date.
干预措施: Stereotactic Ablative Radiotherapy (Radiation)
结局指标
主要结局
Objective response rate at 6 months
时间窗: 6 months after the completion of treatment
Objective response rate including complete and partial response based on the MRI evaluation (mRECIST)
次要结局
- 1-year overall survival(1 year after the treatment completion)
- Time to progression(1 year after the treatment completion)
- Time to untreatable progression(1 year after the treatment completion)
- Quality of life assessment by questionnaire at baseline(baseline)
- Quality of life assessment by questionnaire at 2 months(2 months)
- Quality of life assessment by questionnaire at 6 months(6 months after treatment completion)
- Assessment by questionnaires of specific for hepatocarcinoma quality of life at baseline(baseline)
- Assessment by questionnaires of specific for hepatocarcinoma quality of life at 2 months(2 months after treatment completion)
- Assessment by questionnaires of specific for hepatocarcinoma quality of life at 6 months(6 months after treatment completion)
- Overall response rate based on the MRI evaluation in Child Pugh B7 patients(6 months)
- 6-months overall survival(1 year after the treatment completion)
- Acute toxicities(6 months after treatment completion)
- Late toxicities(6 months after treatment completion)