Back to resultsTACE vs TACE+SBRT for Unresectable Hepatocellular Cancer (TACE-SBRT)
Primary Purpose
Carcinoma, Hepatocellular
Status
Recruiting
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
SBRT
TACE
Sorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of HCC. Tissue diagnosis is not mandatory however desirable. In the absence of tissue diagnosis imaging findings characteristic of HCC will be used. i.e. in high risk population a nodule with arterial phase enhancement and wash out during portovenous phase will be considered as diagnostic of HCC. In patients where one imaging is not conclusive another imaging modality will be used. However if second imaging is also inconclusive and Alpha Feto Protein (AFP) is within the nondiagnostic or borderline range than tissue diagnosis will be deemed mandatory.
- Barcelona Stage B/ Barcelona A not deemed suitable for Sx or refuse surgery. Child Pugh A/Select Child Pugh B (score7/10).
- Eastern Cooperative Oncology Group Performance Status 0-1.
- Total number of measurable target lesions 2 or less than 2, can be encompassed within a single hepatic field or 2 different hepatic fields without exceeding safe dose limit constraints.
- Optimal predicted liver volume reserve >700 cc. No Contraindication for TACE. Tumor considered to be sufficiently away from GI structures to deliver safe radiation dose (>1 cm).
- Willing for molecular banking of tumour tissue (optional).
Exclusion Criteria:
- Metastatic or nodal disease on staging investigations.
- Child C Cirrhosis or previous history of liver failure. Expected life span <6 months.
- Active variceal bleeding or other signs of hepatic decompensation.
- Portal venous thrombosis rendering patients unsuitable for TACE. However if pt is suitable for superselective TACE then can be considered for trial inclusion.
Sites / Locations
- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial CentreRecruiting
- Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
DEB TACE Arm
DEB-TACE+SBRT arm
Arm Description
Patients randomized to drug eluting beads(DEB) TACE arm will undergo 3 cycles of DEB-TACE (100 mg of doxorubicin drug eluting beads which will be repeated after 4-6 weeks. CT/MRI will be repeated prior to each cycle. Sorafenib will be omitted on the day of TACE and will be reinitiated after the TACE procedure. After completing all TACE cycles patients will continue to be on sorafenib till progression, or 12 months whichever is later, or in patients who fail to tolerate it after dose modifications. Hepatobiliary CTCAE will be completed at baseline, at each TACE cycle and subsequently at each follow up. QOL will be evaluated at the same time and also at two months after completing all sessions of TACE (matched time point with completion of SBRT in interventional arm)
Patients randomized to DEB TACE/SBRT arm will undergo DEB-TACE as in standard arm. SBRT will be initiated 4-6 weeks after last TACE procedure. During this period patients will stop Sorafenib. SBRT once initiated will continue for 2-2.5 weeks. Sorafenib will be reinitiated 4 weeks after SBRT completion and will continue to be administered till progression or 12 months whichever is earlier, or in patients who fail to tolerate it after dose modifications. QOL will be evaluated at baseline, before each cycle of TACE, 1 month after SBRT and three monthly thereafter. Hepatobiliary CTCAE will be completed at baseline, after each TACE, before SBRT and after completion of SBRT and subsequently at each follow up.
Outcomes
Primary Outcome Measures
In-field Progression Free Survival
The trial is designed to assess a benefit in in-field progression free survival. The principal investigator would assess the study results 24 months after last accrual.
Secondary Outcome Measures
Cause Specific Survival
Will compare the cause specific survival between both the arms
Response assessment after treatment
Using modified Response Evaluation Criteria in Solid Tumors scoring, radiological response to treatment will be assessed between both the arms.
Quality of Life Assessment of patients over a period of time
European Organisation for Research and Treatment of Cancer (EORTC) Study Group on Quality of Life has developed the Quality of life questionaires (QLQ) which are EORTC QLQ-C30 and the hepatocellular carcinoma specific EORTC QLQ-HCC 18 consisting in a modular system for assessing the quality of life of cancer patients in clinical research. EORTC QLQ-HCC 18 is an 18-item questionnaire designed to be used along with the 30-item EORTC QLQ-C30 Each item will be scored according to the EORTC guidelines
Toxicity Assessment
Assessment will be done according to CTCAE v4.0
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02794337
Brief Title
TACE vs TACE+SBRT for Unresectable Hepatocellular Cancer
Acronym
TACE-SBRT
Official Title
Integrated Phase II/III Randomized Control Trial of Transarterial Chemoembolisation Alone or in Combination With Stereotactic Body Radiation in Patients With Unresectable Hepatocellular Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2014 (undefined)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tata Memorial Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Vast majority of patients with hepatocellular carcinoma (HCC) present with unresectable disease. In the last decade results of randomized trials and a subsequent metaanalyses established transarterial chemoembolization (TACE) or systemic chemotherapy (sorafenib) as standard of care. However, TACE alone is not a curative approach. The two year survival following TACE ranges from 31-63% with almost 100% patients developing disease progression after treatment. There is need to investigate additional therapeutic options that would consolidate the initial response to TACE. A recent metaanalyses concluded that addition of high dose radiation to TACE results in 10-35% improvement in two year overall survival. However as results of metaanalyses were based on studies with small sample size, unclear randomization procedure and heterogenous dose of radiation, the need for conducting a high quality randomized study was highlighted The present study is designed to investigate the role of high dose conformal radiation as consolidation therapy after TACE in patients with nonmetastatic unresectable HCC.
Detailed Description
Resection or liver transplant is the only curative treatment in patients with hepatocellular carcinoma (HCC) however a vast majority of patients present with unresectable disease. In the last decade results of randomized trials and a subsequent metaanalyses established transarterial chemoembolization (TACE) as standard of care in patients with Barcelona Clinic Liver Cancer (BCLC) stage B. However, TACE alone is not a curative approach. The two year survival following TACE ranges from 31-63% with almost 100% patients developing disease progression after treatment. There is need to investigate additional therapeutic options that would consolidate the initial response to TACE. A recent metaanalyses including 17 trials (5 randomized and 12 non randomized studies) concluded that addition of high dose radiation to TACE results in upto 10-35% improvement in two year overall survival. However as results of metaanalyses were based on studies with small sample size, unclear randomization procedure and heterogenous dose of radiation, the need for conducting a high quality randomized study was highlighted. The present study is designed to investigate the role of high dose conformal radiation as consolidation therapy after TACE in patients with nonmetastatic unresectable HCC.
With an integrated phase II/III design the study investigates the impact of local radiation therapy on infield progression free survival in patients with locally advanced unresectable HCC.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
67 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
DEB TACE Arm
Arm Type
Active Comparator
Arm Description
Patients randomized to drug eluting beads(DEB) TACE arm will undergo 3 cycles of DEB-TACE (100 mg of doxorubicin drug eluting beads which will be repeated after 4-6 weeks. CT/MRI will be repeated prior to each cycle. Sorafenib will be omitted on the day of TACE and will be reinitiated after the TACE procedure. After completing all TACE cycles patients will continue to be on sorafenib till progression, or 12 months whichever is later, or in patients who fail to tolerate it after dose modifications. Hepatobiliary CTCAE will be completed at baseline, at each TACE cycle and subsequently at each follow up. QOL will be evaluated at the same time and also at two months after completing all sessions of TACE (matched time point with completion of SBRT in interventional arm)
Arm Title
DEB-TACE+SBRT arm
Arm Type
Experimental
Arm Description
Patients randomized to DEB TACE/SBRT arm will undergo DEB-TACE as in standard arm. SBRT will be initiated 4-6 weeks after last TACE procedure. During this period patients will stop Sorafenib. SBRT once initiated will continue for 2-2.5 weeks. Sorafenib will be reinitiated 4 weeks after SBRT completion and will continue to be administered till progression or 12 months whichever is earlier, or in patients who fail to tolerate it after dose modifications. QOL will be evaluated at baseline, before each cycle of TACE, 1 month after SBRT and three monthly thereafter. Hepatobiliary CTCAE will be completed at baseline, after each TACE, before SBRT and after completion of SBRT and subsequently at each follow up.
Intervention Type
Radiation
Intervention Name(s)
SBRT
Other Intervention Name(s)
Stereotactic Ablative Radiation
Intervention Description
Intervention involves administering high precision radiation to the tumour in 6-8 fractions over 2-2.5 weeks
Intervention Type
Procedure
Intervention Name(s)
TACE
Other Intervention Name(s)
Transarterial chemoembolisation
Intervention Description
Involves catheterization of the tumour feeding vessels and injecting 100 mg of doxorubicin drug eluting beads. Maximum 3 TACE procedures are done
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Other Intervention Name(s)
Tyrosine Kinase Inhibitor
Intervention Description
Sorafenib will be initiated 2 weeks before 1st TACE at a dose considered appropriate by the treating clinician. Though 400 mg bid is the recommended dose a lower dose may be used as per the judgement of treating clinician. It will be omitted on the days of TACE and SBRT. Sorafenib will be reinitiated 4 weeks after SBRT completion and will continue to be administered till progression or 12 months whichever is earlier. Sorafenib can however be stopped in patients who fail to tolerate sorafenib even after dose modifications.
Primary Outcome Measure Information:
Title
In-field Progression Free Survival
Description
The trial is designed to assess a benefit in in-field progression free survival. The principal investigator would assess the study results 24 months after last accrual.
Time Frame
Upto 24 months
Secondary Outcome Measure Information:
Title
Cause Specific Survival
Description
Will compare the cause specific survival between both the arms
Time Frame
Upto 24 months
Title
Response assessment after treatment
Description
Using modified Response Evaluation Criteria in Solid Tumors scoring, radiological response to treatment will be assessed between both the arms.
Time Frame
Upto 24 months
Title
Quality of Life Assessment of patients over a period of time
Description
European Organisation for Research and Treatment of Cancer (EORTC) Study Group on Quality of Life has developed the Quality of life questionaires (QLQ) which are EORTC QLQ-C30 and the hepatocellular carcinoma specific EORTC QLQ-HCC 18 consisting in a modular system for assessing the quality of life of cancer patients in clinical research. EORTC QLQ-HCC 18 is an 18-item questionnaire designed to be used along with the 30-item EORTC QLQ-C30 Each item will be scored according to the EORTC guidelines
Time Frame
Upto 24 months
Title
Toxicity Assessment
Description
Assessment will be done according to CTCAE v4.0
Time Frame
Upto 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of HCC. Tissue diagnosis is not mandatory however desirable. In the absence of tissue diagnosis imaging findings characteristic of HCC will be used. i.e. in high risk population a nodule with arterial phase enhancement and wash out during portovenous phase will be considered as diagnostic of HCC. In patients where one imaging is not conclusive another imaging modality will be used. However if second imaging is also inconclusive and Alpha Feto Protein (AFP) is within the nondiagnostic or borderline range than tissue diagnosis will be deemed mandatory.
Barcelona Stage B/ Barcelona A not deemed suitable for Sx or refuse surgery. Child Pugh A/Select Child Pugh B (score7/10).
Eastern Cooperative Oncology Group Performance Status 0-1.
Total number of measurable target lesions 2 or less than 2, can be encompassed within a single hepatic field or 2 different hepatic fields without exceeding safe dose limit constraints.
Optimal predicted liver volume reserve >700 cc. No Contraindication for TACE. Tumor considered to be sufficiently away from GI structures to deliver safe radiation dose (>1 cm).
Willing for molecular banking of tumour tissue (optional).
Exclusion Criteria:
Metastatic or nodal disease on staging investigations.
Child C Cirrhosis or previous history of liver failure. Expected life span <6 months.
Active variceal bleeding or other signs of hepatic decompensation.
Portal venous thrombosis rendering patients unsuitable for TACE. However if pt is suitable for superselective TACE then can be considered for trial inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Supriya Chopra, MD
Phone
09930958309
Email
supriyasastri@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Supriya Chopra, MD
Phone
09930958309
Email
schopra@actrec.gov.in
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Supriya Chopra, MD
Organizational Affiliation
ACTREC,Tata Memorial Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre
City
Navi Mumbai
State/Province
Maharashtra
ZIP/Postal Code
410210
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Supriya Chopra, MD,DNB
Phone
022-27405000
Ext
5510
Email
schopra@actrec.gov.in
Facility Name
Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre
City
Navi Mumbai
State/Province
Maharashtra
ZIP/Postal Code
410210
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Supriya Chopra, MD
Phone
91-22-27405000
Ext
5491
Email
schopra@actrec.gov.in
First Name & Middle Initial & Last Name & Degree
Supriya Chopra, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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TACE vs TACE+SBRT for Unresectable Hepatocellular Cancer
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