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

NCT ID: NCT03535259

Last Updated: 2024-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-08
• Study Completion Date: 2021-06-01

Brief Summary

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.

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.

Conditions

Hepatocellular Carcinoma, Radiotherapy, Sorafenib

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

concurrent sorafenib and IMRT, followed sorafenib maintenance

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

BO CHEN

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Bo Chen

Beijing, Beijing Municipality, China

Countries

China

References

Zhai Y, Wang L, Zhao H, Wu F, Xin L, Ye F, Sun W, Song Y, Niu L, Zeng H, Wang J, Tang Y, Song Y, Liu Y, Fang H, Lu N, Jing H, Qi S, Zhang W, Wang S, Li YX, Wu J, Chen B. Phase II study with sorafenib plus radiotherapy for advanced HCC with portal and/or hepatic vein tumor thrombosis. JHEP Rep. 2024 Nov 28;7(3):101287. doi: 10.1016/j.jhepr.2024.101287. eCollection 2025 Mar.

Reference Type: DERIVED

PMID: 39980754 (View on PubMed)

Other Identifiers

NCC201803020

Identifier Type: -

Identifier Source: org_study_id