Phase II Study of Concurrent Sorafenib and Intensity-modulated Radiotherapy (IMRT) for Advanced Hepatocellular Carcinoma (SIRAHCC)

This is a single-arm phase II clinical trial to investigate the efficacy and toxicity of concurrent sorafenib and intensity-modulated radiotherapy (IMRT) for advanced hepatocellular carcinoma with portal vein or hepatic vein tumor thrombosis or lymph node involved. Eligibility patients will receive IMRT to hepatic primary tumor, vein tumor thrombosis, and metastasis lymph node with concurrently sorafenib with a dose of 400mg twice daily. Prescription of IMRT will be a conventional fraction dose of 2Gy to a total dose of 40 to 60Gy. Sorafenib will be maintained with a dose of 400mg twice daily after IMRT until disease progression, or unacceptable adverse events. Six months of sorafenib maintenance is recommended.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma, Radiotherapy, Sorafenib
• Intervention / Treatment: Radiation: concurrent sorafenib and IMRT, followed sorafenib maintenance

Detailed Description

With the clinical application of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT), radiotherapy (RT) has shown important role in the treatment of hepatocellular carcinoma (HCC). Meta-analysis has demonstrated that transcatheter arterial chemoembolization (TACE) combined RT was more therapeutically beneficial than TACE alone. Especially for advanced disease with portal vein tumor thrombosis (PVTT), or hepatic vein tumor thrombosis, or lymph node involved, RT was more effective than other treatment methods. Previous studies had showed that RT could receive response rate of 50% to 60% for HCC with PVTT. But for those patients, high accidence of out RT field failure of liver and distance metastasis was found. Effective systemic therapy was necessary to advanced HCC. Based on two phase III trials, sorafenib was recommended as systemic therapy to advanced HCC. But tumor response rate of sorafenib alone was only 2.3-3% by RICIST criteria. More than half of patients was received survival benefit by maintaining in stable disease. It is feasible to improve survival by combining IMRT and sorafenib for advanced HCC with portal vein tumor thrombosis (PVTT), or hepatic vein tumor thrombosis, or lymph node involved. In addition, it was demonstrated that sorafenib could potentiate irradiation in HCC cell lines through inhibiting radiation-induced proliferation and DNA repair and promoting radiation-induced apoptosis.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Bo Chen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinical or histologic diagnosis of Hepatocellular carcinoma (HCC)
2. Aged between 18 and 80 years
3. ECOG 0-1
4. Liver-GTV>700ml
5. BCLC stage C, HCC with portal vein or hepatic vein tumor thrombosis or lymph node involved (LN involved can be included one treatment planning)
6. Estimated life expectancy > 3 months
7. Child-Pugh Score: A5-B8
8. Hepatic function: alanine transaminase (ALT) and aspartate transaminase (AST)≤ 1.5 times ULN; or ALT ≤ ULN and AST≤ 6 times ULN exclude possibility of heart disease
9. Renal function: creatinine (CRE) and blood urea nitrogen (BUN)≤ 1.5 times ULN
10. Blood routine examination: Hb≥80g/L, ANC≥1.0×109 /L, PLT≥40×109 /L
11. Voluntary to participate and sign informed consent

Exclusion Criteria:

1. Had prior abdominal irradiation
2. Had prior liver transplantation
3. Had serious myocardial disease or renal failure
4. Pregnant, breast feeding, or unwilling to use adequate contraception
5. Known hypersensitivity to sorafenib

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib and IMRT; Concurrent sorafenib and IMRT, followed sorafenib maintenance for advanced hepatocellular carcinoma with portal vein or hepatic vein tumor thrombosis or lymph node involved	Radiation: concurrent sorafenib and IMRT, followed sorafenib maintenance; IMRT 40-60Gy/20-30f; concurrent sorafenib 400mg bid po (it can be given to patients in four weeks before IMRT is applied, so that it can control disease during waiting for IMRT); maintenance sorafenib 400mg bid po until disease progress or unacceptable adverse events; six months is recommended but not mandatory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MST	Median Survival Time (MST) was defined as the duration from the date of patient recruited to the date of death from any cause	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTP	Time to Progression (TTP) was defined as the duration from the date of patient recruited to the first progress at any site or the date of death	24 months
Rate of III-IV grade adverse events	Adverse events was evaluated during received protocol therapy according to CTCAE 4.03	up to 24 months
ORR	Overall Response Rate (ORR) was defined as the total of CR (Complete Response) and PR (Partial Response). CR and PR were assessed by independent reviewers according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR evaluated in 1 to 3 months after the completion of IMRT.	Assessment in 1 to 3 months after IMRT

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2018
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: May 12, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; sorafenib; lymph node metastasis; portal vein thrombosis; intensity-modulated radiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCC201803020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No