Carcinoma, HepatocellularPhase 2/3TACE-SBRTNCT02794337
TACE vs TACE+SBRT for Unresectable Hepatocellular Cancer
A Phase 2/3 study testing SBRT, TACE and Sorafenib in people with Carcinoma, Hepatocellular, run by Tata Memorial Hospital at 2 sites in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- SBRT, TACE and Sorafenib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 2 sitesIndia
- Study dates
- Dec 2014to Jan 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
India2 sites, 2 recruiting
- Recruiting
Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre
Navi Mumbai, Maharashtra, 410210
Supriya Chopra, MD,DNB, 022-27405000 ext. 5510, schopra@actrec.gov.in
- Recruiting
Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre
Navi Mumbai, Maharashtra, 410210
Dr Supriya Chopra, MD, 91-22-27405000 ext. 5491, schopra@actrec.gov.in
Supriya Chopra, MD
About this study
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
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.
Read the 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.
- Conditions
- Carcinoma, Hepatocellular
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
Also called Stereotactic Ablative Radiation
Intervention involves administering high precision radiation to the tumour in 6-8 fractions over 2-2.5 weeks
TACEProcedure or surgery
Also called Transarterial chemoembolisation
Involves catheterization of the tumour feeding vessels and injecting 100 mg of doxorubicin drug eluting beads. Maximum 3 TACE procedures are done
SorafenibDrug
Also called Tyrosine Kinase Inhibitor
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.
| Study group | Role | What they receive |
|---|---|---|
| DEB TACE Arm | Active comparator | 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) Receives: Procedure: TACE; Drug: Sorafenib |
| DEB-TACE+SBRT arm | Experimental | 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. Receives: Radiation: SBRT; Procedure: TACE; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Upto 24 months
Secondary outcomes (4)
Cause Specific Survival
Will compare the cause specific survival between both the arms
Measured: Upto 24 months
Response assessment after treatment
Using modified Response Evaluation Criteria in Solid Tumors scoring, radiological response to treatment will be assessed between both the arms.
Measured: Upto 24 months
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
Measured: Upto 24 months
Toxicity Assessment
Assessment will be done according to CTCAE v4.0
Measured: Upto 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2016 (estimated)
- Study startDec 2014
- Primary completionJan 2024 (estimated)
- Study completionJan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Supriya Sastri (chopra), Tata Memorial Hospital
- Investigators
- Supriya Chopra, MD, Principal investigator, ACTREC,Tata Memorial Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02794337
- Sponsor's protocol ID
- TMC IEC III 91
- Acronym
- TACE-SBRT
- Status last verified
- Apr 2022
- First submitted
- 8 Mar 2016
- Last updated
- 27 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02794337
- Acronym / sponsor ID
- TACE-SBRT / TMC IEC III 91
- Conditions
- Carcinoma, Hepatocellular
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 67 participants (estimated)
- Lead sponsor
- Tata Memorial HospitalOther government
- Study start
- Dec 2014
- Primary completion
- Jan 2024 (estimated)
- Study completion
- Jan 2024 (estimated)
- First posted
- 9 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DEB TACE Arm | Active comparator | Procedure: TACE, Drug: SorafenibPatients 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) |
| DEB-TACE+SBRT arm | Experimental | Radiation: SBRT, Procedure: TACE, Drug: SorafenibPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRTAlso: Stereotactic Ablative RadiationIntervention involves administering high precision radiation to the tumour in 6-8 fractions over 2-2.5 weeks | Radiation | DEB-TACE+SBRT arm |
| TACEAlso: Transarterial chemoembolisationInvolves catheterization of the tumour feeding vessels and injecting 100 mg of doxorubicin drug eluting beads. Maximum 3 TACE procedures are done | Procedure or surgery | DEB TACE Arm, DEB-TACE+SBRT arm |
| SorafenibAlso: Tyrosine Kinase InhibitorSorafenib 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. | Drug | DEB TACE Arm, DEB-TACE+SBRT arm |
Primary outcome
In-field Progression Free Survival
Time frame: Upto 24 months
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.
4 secondary outcomes
Cause Specific Survival
Time frame: Upto 24 months
Response assessment after treatment
Time frame: Upto 24 months
Quality of Life Assessment of patients over a period of time
Time frame: Upto 24 months
Toxicity Assessment
Time frame: Upto 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Supriya Chopra, MD principal investigator
ACTREC,Tata Memorial Centre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing SBRT, TACE and Sorafenib in people with Carcinoma, Hepatocellular, run by Tata Memorial Hospital at 2 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Supriya Chopra, MD (09930958309, supriyasastri@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In-field Progression Free Survival (time frame: Upto 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.