Clinical trial NCT02794337: TACE vs TACE+SBRT for Unresectable Hepatocellular Cancer
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
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
First posted: 2016-06-09
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: In-field Progression Free Survival
timeFrame: Upto 24 months
Secondary outcomes:
measure: Cause Specific Survival
timeFrame: Upto 24 months
measure: Response assessment after treatment
timeFrame: Upto 24 months
measure: Quality of Life Assessment of patients over a period of time
timeFrame: Upto 24 months
measure: Toxicity Assessment
timeFrame: Upto 24 months
Other outcomes:
Locations:
city: Navi Mumbai
country: India
facility: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre
state: Maharashtra
city: Navi Mumbai
country: India
facility: Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre
state: Maharashtra
Study officials:
affiliation: ACTREC,Tata Memorial Centre
name: Supriya Chopra, MD
role: PRINCIPAL_INVESTIGATOR
References: