TACE vs TACE+SBRT for Unresectable Hepatocellular Cancer

NCT02794337 | Unknown Phase 2 DMC

• 1 other identifier: TMC IEC III 91
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 2

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.

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Cause Specific Survival

  Upto 24 months

• Response assessment after treatment

  Upto 24 months

• Quality of Life Assessment of patients over a period of time

  Upto 24 months

• Toxicity Assessment

  Upto 24 months

Study Arms (2)

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)

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.

Radiation: SBRT; Procedure: TACE; Drug: Sorafenib

Interventions

SBRT RADIATION

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

Also known as: Stereotactic Ablative Radiation

DEB-TACE+SBRT arm

TACE PROCEDURE

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

Also known as: Transarterial chemoembolisation

DEB TACE Arm; DEB-TACE+SBRT arm

Sorafenib DRUG

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.

Also known as: Tyrosine Kinase Inhibitor

DEB TACE Arm; DEB-TACE+SBRT arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tata Memorial Hospital: lead

Study Sites (2)

Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre

Navi Mumbai, Maharashtra, 410210, India

RECRUITING

Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre

Navi Mumbai, Maharashtra, 410210, India

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Supriya Chopra, MD

  ACTREC,Tata Memorial Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Supriya Chopra, MD

CONTACT

09930958309; supriyasastri@gmail.com

Supriya Chopra, MD

CONTACT

09930958309; schopra@actrec.gov.in

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Radiation Oncology

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: June 9, 2016
• Study Start: December 1, 2014
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: April 27, 2022

Record last verified: 2022-04

Locations

IN (2)