Back to resultsClinical Trial Comparing TACE With TACE + SABR in Stage BCLC B HCC (HepSTAR) (HepSTAR)
Primary Purpose
Liver Neoplasms, Hepatocellular Cancer
Status
Terminated
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Trans-arterial Chemo-Embolization
Doxorubicin
Stereotactic Ablative Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Liver Neoplasms focused on measuring Hepatocellular cancer, Stereotactic Body Radiotherapy, Chemoembolization, Therapeutic
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
- 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
Sites / Locations
- Hôpital de JOLIMONT
- Centre Hospitalier Universitaire/CHC Saint Joseph
- Cliniques Universitaires Saint Luc
- Institut Jules Bordet/Hôpital Erasme
- Clinique et Maternité Sainte Elisabeth/CHU Mont Godinne
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Trans-Arterial Chemo-embolization (TACE)
TACE+Stereotactic Ablative Radiotherapy
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Objective response rate at 6 months
Objective response rate including complete and partial response based on the MRI evaluation (mRECIST)
Secondary Outcome Measures
Time to progression
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
defined as the time between the end of treatment and the occurrence of untreatable intra-hepatic disease
6-months overall survival
defined as survival rate of patients at 6months after the end of treatment
1-year overall survival
defined as survival rate of patients at 1 year after the end of treatment
Acute toxicities
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
Late toxic events will have to be described and recorded in accordance with the CTCAE 4.03 (Common Terminology Criteria for Adverse events).
Quality of life assessment by questionnaire at 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
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
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
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
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
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
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.
Full Information
NCT ID
NCT02958163
First Posted
October 26, 2016
Last Updated
November 6, 2017
Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborators
Erasme University Hospital, Jules Bordet Institute, University of Liege, Clinique Saint Joseph, Liège, Centre Hospitalier Universitaire UCLouvain Namur
1. Study Identification
Unique Protocol Identification Number
NCT02958163
Brief Title
Clinical Trial Comparing TACE With TACE + SABR in Stage BCLC B HCC (HepSTAR)
Acronym
HepSTAR
Official Title
Randomized Controlled Phase II Trial Comparing Trans-Arterial Chemo-Embolization (TACE) With TACE Plus Stereotactic Ablative Radiotherapy (SABR) in Stage BCLC B Hepatocarcinoma (HepSTAR)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
lack of recruitment
Study Start Date
February 20, 2017 (Actual)
Primary Completion Date
October 17, 2017 (Actual)
Study Completion Date
October 17, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborators
Erasme University Hospital, Jules Bordet Institute, University of Liege, Clinique Saint Joseph, Liège, Centre Hospitalier Universitaire UCLouvain Namur
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Neoplasms, Hepatocellular Cancer
Keywords
Hepatocellular cancer, Stereotactic Body Radiotherapy, Chemoembolization, Therapeutic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Trans-Arterial Chemo-embolization (TACE)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
TACE+Stereotactic Ablative Radiotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Trans-arterial Chemo-Embolization
Other Intervention Name(s)
TACE
Intervention Description
Trans-Arterial Chemo-Embolization will be performed with Doxorubicin-Eluting-Beads (DEB-TACE). It will be performed in each arm of treatment.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
DEB-TACE
Intervention Description
Drug-eluting Bead for Trans Arterial Chemo-Embolization will be loaded with Doxorubicin.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Ablative Radiotherapy
Other Intervention Name(s)
SABR
Intervention Description
SABR schemes will be adapted according to the CP score and the vicinity of surrounding organs at risk. These are the different schemes proposed in this trial:
48Gy = 3x16Gy BED 124.8Gy ( α/β=10) 50Gy = 5x10Gy BED 100Gy ( α/β=10) 48Gy = 6x8Gy BED 86.4Gy ( α/β=10) 40Gy = 5x8Gy BED 72Gy ( α/β=10)
For patients with Child-Pugh (CP) A cirrhosis : the choice of the scheme will be left to each physician. The highest BED should be favored if dose constraints to the organs at risk are respected.
For patients with CP B cirrhosis : only the latter scheme will be allowed: 40Gy = 5x8Gy.
Primary Outcome Measure Information:
Title
Objective response rate at 6 months
Description
Objective response rate including complete and partial response based on the MRI evaluation (mRECIST)
Time Frame
6 months after the completion of treatment
Secondary Outcome Measure Information:
Title
Time to progression
Description
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 Frame
1 year after the treatment completion
Title
Time to untreatable progression
Description
defined as the time between the end of treatment and the occurrence of untreatable intra-hepatic disease
Time Frame
1 year after the treatment completion
Title
6-months overall survival
Description
defined as survival rate of patients at 6months after the end of treatment
Time Frame
1 year after the treatment completion
Title
1-year overall survival
Description
defined as survival rate of patients at 1 year after the end of treatment
Time Frame
1 year after the treatment completion
Title
Acute toxicities
Description
Acute toxic events will have to be described and recorded in accordance with the CTCAE 4.03 (Common Terminology Criteria for Adverse events).
Time Frame
6 months after treatment completion
Title
Late toxicities
Description
Late toxic events will have to be described and recorded in accordance with the CTCAE 4.03 (Common Terminology Criteria for Adverse events).
Time Frame
6 months after treatment completion
Title
Quality of life assessment by questionnaire at baseline
Description
Quality of life will be assessed by questionnaires: EORTC QLQC30. The investigators will ask each patient to answer to these questionnaires once at randomization.
Time Frame
baseline
Title
Quality of life assessment by questionnaire at 2 months
Description
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
Time Frame
2 months
Title
Quality of life assessment by questionnaire at 6 months
Description
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
Time Frame
6 months after treatment completion
Title
Assessment by questionnaires of specific for hepatocarcinoma quality of life at baseline
Description
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.
Time Frame
baseline
Title
Assessment by questionnaires of specific for hepatocarcinoma quality of life at 2 months
Description
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
Time Frame
2 months after treatment completion
Title
Assessment by questionnaires of specific for hepatocarcinoma quality of life at 6 months
Description
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
Time Frame
6 months after treatment completion
Title
Overall response rate based on the MRI evaluation in Child Pugh B7 patients
Description
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.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Immuno-histochemical detection of tumoral markers on biopsy (AFP/CK19/DCP)
Description
Differents markers will be checked on biopsy (AFP = alpha foetoprotein/ CK19 = cytokeratin 19/ DPC= Des Carboxy prothrombin).
Time Frame
at time of biopsy
Title
Baseline biological detection of tumoral marker(s) : AFP +/- DCP
Description
Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).
Time Frame
at baseline
Title
Biological detection of tumoral marker(s) (AFP +/- DCP) at 2 months after treatment
Description
Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).
Time Frame
2 months after treatment completion
Title
Biological detection of tumoral marker(s) (AFP +/- DCP) at 4 months after treatment
Description
Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).
Time Frame
4 months after treatment completion
Title
Biological detection of tumoral marker(s) (AFP +/- DCP) at 6 months after treatment
Description
Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).
Time Frame
6 months after treatment completion
Title
MRI description of tumors at the hepatobiliary phase at baseline
Description
immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected
Time Frame
at baseline
Title
MRI description of tumors at the hepatobiliary phase at 2 months after treatment
Description
immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected
Time Frame
2 months after treatment completion
Title
MRI description of tumors at the hepatobiliary phase at 6 months after treatment
Description
immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected
Time Frame
6 months after treatment completion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xavier GEETS
Organizational Affiliation
Cliniques Universitaires Saint Luc/MIRO
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ivan BORBATH
Organizational Affiliation
Cliniques universitaires Saint-Luc
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital de JOLIMONT
City
Jolimont
State/Province
Hainaut
ZIP/Postal Code
7100
Country
Belgium
Facility Name
Centre Hospitalier Universitaire/CHC Saint Joseph
City
Liege
State/Province
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Cliniques Universitaires Saint Luc
City
Brussels
State/Province
Woluwé Saint Lambert
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Institut Jules Bordet/Hôpital Erasme
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Clinique et Maternité Sainte Elisabeth/CHU Mont Godinne
City
Namur
ZIP/Postal Code
5000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Every participant data will be anonymized for the trial purpose.
Learn more about this trial
Clinical Trial Comparing TACE With TACE + SABR in Stage BCLC B HCC (HepSTAR)
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