Clinical Trial Comparing TACE With TACE + SABR in Stage BCLC B HCC (HepSTAR)
- Conditions
- Liver NeoplasmsHepatocellular Cancer
- Interventions
- Procedure: Trans-arterial Chemo-EmbolizationDrug: DoxorubicinRadiation: Stereotactic Ablative Radiotherapy
- Registration Number
- NCT02958163
- Lead Sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
-
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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trans-Arterial Chemo-embolization (TACE) Trans-arterial Chemo-Embolization 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. TACE+Stereotactic Ablative Radiotherapy Trans-arterial Chemo-Embolization 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. TACE+Stereotactic Ablative Radiotherapy Doxorubicin 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. TACE+Stereotactic Ablative Radiotherapy 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. Trans-Arterial Chemo-embolization (TACE) Doxorubicin 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.
- Primary Outcome Measures
Name Time Method Objective response rate at 6 months 6 months after the completion of treatment Objective response rate including complete and partial response based on the MRI evaluation (mRECIST)
- Secondary Outcome Measures
Name Time Method 1-year overall survival 1 year after the treatment completion defined as survival rate of patients at 1 year after the end of treatment
Time to progression 1 year after the treatment completion defined as the time between the end of treatment and the occurrence of a local recurrence. The diagnoses of another intra- or extra-hepatic lesion of HCC will not be considered as progression
Time to untreatable progression 1 year after the treatment completion defined as the time between the end of treatment and the occurrence of untreatable intra-hepatic disease
Quality of life assessment by questionnaire at baseline baseline Quality of life will be assessed by questionnaires: EORTC QLQC30. The investigators will ask each patient to answer to these questionnaires once at randomization.
Quality of life assessment by questionnaire at 2 months 2 months Quality of life will be assessed by questionnaires: EORTC QLQC30. The investigators will ask each patient to answer to these questionnaires 2 months after treatment completion
Quality of life assessment by questionnaire at 6 months 6 months after treatment completion Quality of life will be assessed by questionnaires: EORTC QLQC30. The investigators will ask each patient to answer to these questionnaires 6 months after treatment completion
Assessment by questionnaires of specific for hepatocarcinoma quality of life at baseline baseline Quality of life will be assessed by questionnaires specific for patients with hepatocarcinoma:EORTC QLQH18. The investigators will ask each patient to answer to these questionnaires once at randomization.
Assessment by questionnaires of specific for hepatocarcinoma quality of life at 2 months 2 months after treatment completion Quality of life will be assessed by questionnaires specific for patients with hepatocarcinoma:EORTC QLQH18. The investigators will ask each patient to answer to these questionnaires 2 months after treatment completion
Assessment by questionnaires of specific for hepatocarcinoma quality of life at 6 months 6 months after treatment completion Quality of life will be assessed by questionnaires specific for patients with hepatocarcinoma:EORTC QLQH18. The investigators will ask each patient to answer to these questionnaires 6 months after treatment completion
Overall response rate based on the MRI evaluation in Child Pugh B7 patients 6 months As the choice of the irradiation scheme will be influenced by the severity of the underlying cirrhosis with a Child Pugh score B7, the overall response rate in this specific kind of patients will be separately measured besides the overall response rate of the whole cohort.
6-months overall survival 1 year after the treatment completion defined as survival rate of patients at 6months after the end of treatment
Acute toxicities 6 months after treatment completion Acute toxic events will have to be described and recorded in accordance with the CTCAE 4.03 (Common Terminology Criteria for Adverse events).
Late toxicities 6 months after treatment completion Late toxic events will have to be described and recorded in accordance with the CTCAE 4.03 (Common Terminology Criteria for Adverse events).
Trial Locations
- Locations (5)
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Woluwé Saint Lambert, Belgium
Clinique et Maternité Sainte Elisabeth/CHU Mont Godinne
🇧🇪Namur, Belgium
Institut Jules Bordet/Hôpital Erasme
🇧🇪Brussels, Belgium
Hôpital de JOLIMONT
🇧🇪Jolimont, Hainaut, Belgium
Centre Hospitalier Universitaire/CHC Saint Joseph
🇧🇪Liege, Liège, Belgium