Clinical trial NCT03535259: Phase II Study of Concurrent Sorafenib and Intensity-modulated Radiotherapy (IMRT) for Advanced Hepatocellular Carcinoma
Official title: Phase II Study of Concurrent Sorafenib and Intensity-modulated Radiotherapy (IMRT) for Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma, Radiotherapy, Sorafenib
Keywords: hepatocellular carcinoma
intensity-modulated radiotherapy
sorafenib
portal vein thrombosis
lymph node metastasis
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2018-05-24
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MST
timeFrame: 24 months
Secondary outcomes:
measure: ORR
timeFrame: Assessment in 1 to 3 months after IMRT
measure: TTP
timeFrame: 24 months
measure: Rate of III-IV grade adverse events
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Bo Chen
state: Beijing
Study officials:
References: