TACE vs TACE+SBRT for Unresectable Hepatocellular Cancer

Carcinoma, Hepatocellular Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02794337
• Other study ID #: TMC IEC III 91
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 2014
• Est. completion date: January 2024

Study information

• Verified date: April 2022
• Source: Tata Memorial Hospital
• Contact: Supriya Chopra, MD
• Phone: 09930958309
• Email: supriyasastri[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 67
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Liver Neoplasms

Intervention

Radiation:
• SBRT
Intervention involves administering high precision radiation to the tumour in 6-8 fractions over 2-2.5 weeks

Procedure:
• TACE
Involves catheterization of the tumour feeding vessels and injecting 100 mg of doxorubicin drug eluting beads. Maximum 3 TACE procedures are done

Drug:
• Sorafenib
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.

Locations

Country	Name	City	State
India	Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre	Navi Mumbai	Maharashtra
India	Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre	Navi Mumbai	Maharashtra

Sponsors (1)

Lead Sponsor	Collaborator
Tata Memorial Hospital

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Upto 24 months
Secondary	Cause Specific Survival	Will compare the cause specific survival between both the arms	Upto 24 months
Secondary	Response assessment after treatment	Using modified Response Evaluation Criteria in Solid Tumors scoring, radiological response to treatment will be assessed between both the arms.	Upto 24 months
Secondary	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	Upto 24 months
Secondary	Toxicity Assessment	Assessment will be done according to CTCAE v4.0	Upto 24 months