Ignite Creation Date:
2024-05-06 @ 7:59 PM
Last Modification Date:
2024-10-26 @ 3:18 PM
Study NCT ID:
NCT06218420
Status:
RECRUITING
Last Update Posted:
2024-06-04
First Post:
2023-12-04
Brief Title:
Evaluation of Stereotactic Body Radiotherapy as a Bridge Therapy for Hepatocellular Carcinoma Patients Enlisted for Liver Transplantation
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Evaluation of Stereotactic Body Radiotherapy as a Bridge Therapy for Hepatocellular Carcinoma Patients Enlisted for Liver Transplantation
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TRANSRAD-01
Brief Summary:
The aim of this trial is to carry out the first prospective multicentric study which evaluates the efficacy and the safety of SBRT in HCC patients enlisted for LT and not suitable for other bridging interventional treatments RF or TACE
The incidence of hepatocellular carcinoma HCC is increasing worldwide and is currently the first indication for Liver transplantation LT HCC patients access to LT is not only determined by the underlying liver function but also by the alpha-fetoprotein aFP score which allows to better identify patients with high risk of recurrence LT is the best curative treatment as it can cure both the tumor and the underlying liver disease However the access to LT is limited due to organ shortage and preserved liver function for the majority of the patients with HCC Bridging therapies such as ablation by radiofrequency RF or microwaves or trans-arterial chemoembolization TACE are carried out routinely to prevent the risk of tumor progression and drop-out during the waiting time the drop-out rate being 20 Nevertheless only 50 to 70 of patients in France will have access to these treatments due to specific contraindications
Stereotactic body radiotherapy SBRT has emerged as a non-invasive alternative and potentially efficient treatment of single or bilocular HCC SBRT is a high-precision technique allowing to deliver a precise high dose irradiation on moving intrahepatic lesions RTS is feasible only when the hepatic reserve is sufficient to avoid radic hepatitis
Advantages of SBRT as compared to TACE or RF are 1 to preserve the hepatic artery which can be altered by TACE 2 to allow access to complex tumors locations or superficial lesions not feasible by RF 3 to avoid any tumor spread related to punctures 4 to avoid general anesthesia
However SBRT has not been validated as bridging therapy before LT in a prospective study Thus this study is the first prospective multicentric study to evaluate this treatment modality in HCC patients enlisted for LT not suitable to RF or TACE
The incidence of hepatocellular carcinoma HCC is increasing worldwide and is currently the first indication for Liver transplantation LT HCC patients access to LT is not only determined by the underlying liver function but also by the alpha-fetoprotein aFP score which allows to better identify patients with high risk of recurrence LT is the best curative treatment as it can cure both the tumor and the underlying liver disease However the access to LT is limited due to organ shortage and preserved liver function for the majority of the patients with HCC Bridging therapies such as ablation by radiofrequency RF or microwaves or trans-arterial chemoembolization TACE are carried out routinely to prevent the risk of tumor progression and drop-out during the waiting time the drop-out rate being 20 Nevertheless only 50 to 70 of patients in France will have access to these treatments due to specific contraindications
Stereotactic body radiotherapy SBRT has emerged as a non-invasive alternative and potentially efficient treatment of single or bilocular HCC SBRT is a high-precision technique allowing to deliver a precise high dose irradiation on moving intrahepatic lesions RTS is feasible only when the hepatic reserve is sufficient to avoid radic hepatitis
Advantages of SBRT as compared to TACE or RF are 1 to preserve the hepatic artery which can be altered by TACE 2 to allow access to complex tumors locations or superficial lesions not feasible by RF 3 to avoid any tumor spread related to punctures 4 to avoid general anesthesia
However SBRT has not been validated as bridging therapy before LT in a prospective study Thus this study is the first prospective multicentric study to evaluate this treatment modality in HCC patients enlisted for LT not suitable to RF or TACE
Detailed Description:
Hypothesis for the study
The hypothesis is that SBRT in HCC patients enlisted for LT and not suitable to liver resection RF or TACE is a safe and effective option to bring those patients to LT while limiting HCC progression during waiting time
This study is the first prospective multicentric study to evaluate this treatment modality in this population
Overview of the multimodal management of hepatocellular carcinoma Liver cancer is the fourth cause of cancer-related death GLOBOCAN with an increasing incidence over the last decades
The best curative treatment for HCC remains liver transplantation LT as it can cure both the tumor and the underlying liver disease 5-year survival rates reach 60-70 in patients with HCC after LT However the number of patients waiting for LT is by far exceeding the number of available donors in 2017 there were 24 candidates for one graft ABM Rapport annuel The global organ shortage and the risk of HCC recurrence after LT have therefore been taken into account in the therapeutic algorithm
In France patients access to LT is determined by their liver function assessed by the Model for End-stage Liver Disease MELD Score which determines a national ranking on waiting list for LT depending on the severity of the liver impairment The waiting list is managed by the National Biomédecine Agency Agence de la Biomédecine For HCC patients the access to LT is not only determined by the underlying liver function but also by the alpha-fetoprotein aFP score which allows to better identify patients with high risk of recurrence An aFP Score 2 allows patients access to LT by adding HCC points to the patients national ranking calculation HCC is currently the first indication for LT 32 of LT candidates in France
Despite efforts are made to prioritize HCC patients on waiting list without disadvantaging other patients without HCC the average waiting time for a LT remains 6 months and can go up to 12 months Therefore those patients face a significant risk of tumor progression during the waiting period leading to tragic drop-outs from the waiting list around 20-30 of patients with HCC In this context the transplant community has developed alternatives to prevent disease progression during the waiting period referred to as bridging therapies It is recommended that patients who are expected to wait for more than 6 months for LT should be treated with bridging therapy
The role of bridging therapies during waiting period for liver transplantation It has been demonstrated that reducing the amount of viable tumor in the liver improves the survival post-LT The choice for one bridging therapy over others is made in expert multidisciplinary meetings depending on patients characteristics underlying liver function and HCC features and the range of bridging treatments proposed vary from potentially curative to palliative options not curative Up to date no guidelines are available to decide which patients should receive bridging therapy The American Association for the Study of Liver Diseases AASLD recommended subjecting every patient who is expected to wait for more than 6 months for LT to bridging therapies In France the proportion of patients receiving bridging therapies represents about 50 to 70 of patients enlisted for HCC
The most frequent bridging therapies include Trans arterial Chemo embolization TACE and ablation RF
Focus on SBRT an emerging therapy for HCC SBRT has emerged as a non-invasive alternative and potentially effective treatment of single or bilocular HCC and has been used for advanced-stage HCC as an alternative to TACE prior to be proposed as an alternate bridging therapy SBRT is a high-precision technique allowing to deliver a precise treatment on moving lesions integrating MRI technology in a short time While the radiosensitivity of the liver did not allow the use of conventional radiotherapy for patients on the waiting list for LT until several years ago these new technical developments made it possible to administer hypofractionated external radiation more precisely Therefore this treatment modality is reported in patients with more advanced liver disease that would otherwise not have access to bridging therapy
Advantages of SBRT as compared to TACE or RF are
to preserve the hepatic artery which can be altered by TACE
to allow access to complex tumors locations or superficial lesions not feasible by RF
to avoid any tumor spread related to punctures
to avoid general anesthesia
However SBRT has not been validated as bridging therapy before LT in a prospective study To date data in the literature are heterogeneous mostly based on retrospective studies and small patient number and are not yet robust enough to pave the basement for a randomized trial comparing SBRT to the other bridging therapies for patients with HCC enlisted for LT There is a lack of subgroup analyses of the role of SBRT in previously treated patients by ablationsurgeryTACE or naive patients iethose in whom other bridge therapies are contraindicated that could allow better clarification of SBRT indications as bridge therapy It is also necessary to provide better understanding of imaging response after SBRT and its correlation with liver explant pathological response
Succinct description of the intervention
SBRT is a high-precision technique allowing to deliver a precise high dose irradiation on moving lesions integrating MRI technology in a short time While the radiosensitivity of the liver did not allow the use of radiotherapy for patients on the waiting list for LT until several years ago these new technical developments made it possible to administer the external radiation more precisely Patients will have 3 to 8 sessions delivered in one to three weeks The overall duration is 3 weeks maximum
Summary of the known and foreseeable benefits and risks for the research participants
Foreseable benefits are to provide access to a bridging therapy during waiting time for LT to patients who would not benefit otherwise from a bridging therapy The objective is to prevent HCC progression during waiting time which may result in drop-out from the waiting list and loss of access to a curative treatment
Foreseable risks related to SBRT are toxicity which may be encountered during radiotherapy and which may be related to irradiation Toxicity includes acute and late adverse side effects from 6 months after the end of SBRT
Design of the study Prospective single arm multicentric phase II trial according to a single stage AHerns design
Number of participating sites Fifteen French LT centers trained in the technique of SBRT for HCC Each LT center is paired with a radiation center
Implementation of the study
Screening visit The screening visit will correspond to the multidisciplinary meeting evaluating LT indications and bridging therapy while waiting for LT for HCC patients in each LT center according to standard of care
Inclusion visit and Baseline visit D-30 to D-1 of the first SBRT session
Information and informed consent Information about the study along with usual information on LT will be provided during a consultation by the surgeon or hepatologist then by the radiation oncologist to determine the final eligibility according to technical feasibility and to explain the modalities objectives and possible adverse effects of SBRT
Final consent will be retrieved by the latest specialist seen by the patients before starting SBRT usually the radiation oncologist
Baseline visit D-30 to D-1
During this visit a special attention will be paid to
Clinical examination General performance status PS score jaundice ascites encephalopathy
Calculation of Child-Pugh Score and MELD Score
Laboratory tests required as done in usual care baseline serum liver tests ASAT ALAT gGT PAL albumin bilirubin PT INR serum alpha-foetoprotein baseline blood count and platelets baseline kidney function serum tests creatinine urea Na K
Paraclinical examinations required usual care for HCC exploration MRI liver imaging or Liver CT scan
SBRT M0
Patients will have 3 to 8 sessions delivered in one to three weeks The overall duration is 3 weeks maximum
Patient monitoring between the sessions will be in line with common practice
Follow-up visits after the first session of SBRT and before LT M1 M3 M6 M9 M12 M15 at maximum
Liver transplantation M15 at maximum
Liver transplantation will be performed according to each centers usual practice As the organ allocation is regulated on a national scale by the National Biomedecine Agency ABM patients access to LT will be unchanged
Data collected on standard operative report intervention duration blood loss amount blood products transfusion per-operative incidents reconstruction modalities arterial portal caval biliary reperfusion syndrome at declamping
Data collected during post-LT hospital stay occurrence of early complications arterial biliary parietal digestive and other
Data related to complications that may be related to SBRT will be recorded biliary complications fistulaestenosis arterial complications stenosis caval complications haemorrhagestenosis delayed wound healing
Post liver transplant follow up maximum 39 months after inclusion and within 24 months post LT
The hypothesis is that SBRT in HCC patients enlisted for LT and not suitable to liver resection RF or TACE is a safe and effective option to bring those patients to LT while limiting HCC progression during waiting time
This study is the first prospective multicentric study to evaluate this treatment modality in this population
Overview of the multimodal management of hepatocellular carcinoma Liver cancer is the fourth cause of cancer-related death GLOBOCAN with an increasing incidence over the last decades
The best curative treatment for HCC remains liver transplantation LT as it can cure both the tumor and the underlying liver disease 5-year survival rates reach 60-70 in patients with HCC after LT However the number of patients waiting for LT is by far exceeding the number of available donors in 2017 there were 24 candidates for one graft ABM Rapport annuel The global organ shortage and the risk of HCC recurrence after LT have therefore been taken into account in the therapeutic algorithm
In France patients access to LT is determined by their liver function assessed by the Model for End-stage Liver Disease MELD Score which determines a national ranking on waiting list for LT depending on the severity of the liver impairment The waiting list is managed by the National Biomédecine Agency Agence de la Biomédecine For HCC patients the access to LT is not only determined by the underlying liver function but also by the alpha-fetoprotein aFP score which allows to better identify patients with high risk of recurrence An aFP Score 2 allows patients access to LT by adding HCC points to the patients national ranking calculation HCC is currently the first indication for LT 32 of LT candidates in France
Despite efforts are made to prioritize HCC patients on waiting list without disadvantaging other patients without HCC the average waiting time for a LT remains 6 months and can go up to 12 months Therefore those patients face a significant risk of tumor progression during the waiting period leading to tragic drop-outs from the waiting list around 20-30 of patients with HCC In this context the transplant community has developed alternatives to prevent disease progression during the waiting period referred to as bridging therapies It is recommended that patients who are expected to wait for more than 6 months for LT should be treated with bridging therapy
The role of bridging therapies during waiting period for liver transplantation It has been demonstrated that reducing the amount of viable tumor in the liver improves the survival post-LT The choice for one bridging therapy over others is made in expert multidisciplinary meetings depending on patients characteristics underlying liver function and HCC features and the range of bridging treatments proposed vary from potentially curative to palliative options not curative Up to date no guidelines are available to decide which patients should receive bridging therapy The American Association for the Study of Liver Diseases AASLD recommended subjecting every patient who is expected to wait for more than 6 months for LT to bridging therapies In France the proportion of patients receiving bridging therapies represents about 50 to 70 of patients enlisted for HCC
The most frequent bridging therapies include Trans arterial Chemo embolization TACE and ablation RF
Focus on SBRT an emerging therapy for HCC SBRT has emerged as a non-invasive alternative and potentially effective treatment of single or bilocular HCC and has been used for advanced-stage HCC as an alternative to TACE prior to be proposed as an alternate bridging therapy SBRT is a high-precision technique allowing to deliver a precise treatment on moving lesions integrating MRI technology in a short time While the radiosensitivity of the liver did not allow the use of conventional radiotherapy for patients on the waiting list for LT until several years ago these new technical developments made it possible to administer hypofractionated external radiation more precisely Therefore this treatment modality is reported in patients with more advanced liver disease that would otherwise not have access to bridging therapy
Advantages of SBRT as compared to TACE or RF are
to preserve the hepatic artery which can be altered by TACE
to allow access to complex tumors locations or superficial lesions not feasible by RF
to avoid any tumor spread related to punctures
to avoid general anesthesia
However SBRT has not been validated as bridging therapy before LT in a prospective study To date data in the literature are heterogeneous mostly based on retrospective studies and small patient number and are not yet robust enough to pave the basement for a randomized trial comparing SBRT to the other bridging therapies for patients with HCC enlisted for LT There is a lack of subgroup analyses of the role of SBRT in previously treated patients by ablationsurgeryTACE or naive patients iethose in whom other bridge therapies are contraindicated that could allow better clarification of SBRT indications as bridge therapy It is also necessary to provide better understanding of imaging response after SBRT and its correlation with liver explant pathological response
Succinct description of the intervention
SBRT is a high-precision technique allowing to deliver a precise high dose irradiation on moving lesions integrating MRI technology in a short time While the radiosensitivity of the liver did not allow the use of radiotherapy for patients on the waiting list for LT until several years ago these new technical developments made it possible to administer the external radiation more precisely Patients will have 3 to 8 sessions delivered in one to three weeks The overall duration is 3 weeks maximum
Summary of the known and foreseeable benefits and risks for the research participants
Foreseable benefits are to provide access to a bridging therapy during waiting time for LT to patients who would not benefit otherwise from a bridging therapy The objective is to prevent HCC progression during waiting time which may result in drop-out from the waiting list and loss of access to a curative treatment
Foreseable risks related to SBRT are toxicity which may be encountered during radiotherapy and which may be related to irradiation Toxicity includes acute and late adverse side effects from 6 months after the end of SBRT
Design of the study Prospective single arm multicentric phase II trial according to a single stage AHerns design
Number of participating sites Fifteen French LT centers trained in the technique of SBRT for HCC Each LT center is paired with a radiation center
Implementation of the study
Screening visit The screening visit will correspond to the multidisciplinary meeting evaluating LT indications and bridging therapy while waiting for LT for HCC patients in each LT center according to standard of care
Inclusion visit and Baseline visit D-30 to D-1 of the first SBRT session
Information and informed consent Information about the study along with usual information on LT will be provided during a consultation by the surgeon or hepatologist then by the radiation oncologist to determine the final eligibility according to technical feasibility and to explain the modalities objectives and possible adverse effects of SBRT
Final consent will be retrieved by the latest specialist seen by the patients before starting SBRT usually the radiation oncologist
Baseline visit D-30 to D-1
During this visit a special attention will be paid to
Clinical examination General performance status PS score jaundice ascites encephalopathy
Calculation of Child-Pugh Score and MELD Score
Laboratory tests required as done in usual care baseline serum liver tests ASAT ALAT gGT PAL albumin bilirubin PT INR serum alpha-foetoprotein baseline blood count and platelets baseline kidney function serum tests creatinine urea Na K
Paraclinical examinations required usual care for HCC exploration MRI liver imaging or Liver CT scan
SBRT M0
Patients will have 3 to 8 sessions delivered in one to three weeks The overall duration is 3 weeks maximum
Patient monitoring between the sessions will be in line with common practice
Follow-up visits after the first session of SBRT and before LT M1 M3 M6 M9 M12 M15 at maximum
Liver transplantation M15 at maximum
Liver transplantation will be performed according to each centers usual practice As the organ allocation is regulated on a national scale by the National Biomedecine Agency ABM patients access to LT will be unchanged
Data collected on standard operative report intervention duration blood loss amount blood products transfusion per-operative incidents reconstruction modalities arterial portal caval biliary reperfusion syndrome at declamping
Data collected during post-LT hospital stay occurrence of early complications arterial biliary parietal digestive and other
Data related to complications that may be related to SBRT will be recorded biliary complications fistulaestenosis arterial complications stenosis caval complications haemorrhagestenosis delayed wound healing
Post liver transplant follow up maximum 39 months after inclusion and within 24 months post LT
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None