External beam radiotherapy for unresectable hepatocellular carcinoma. A multicenter phase I/II trial.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

1.patient must give informed consent before registration
2.confirmed diagnosis of HCC
3.stage: cT2-4, cN0-1, M0 or unresectable cT1,cN0-1,M0
4.cirrhosis Child-Pugh class A or B
5.measurable disease
6.residual liver volume: >= 800 ml or >= 40% of total liver volume
7.WHO 0-2
8.adequate hematological volumes
9.adequate hepatic functions
10.adequate coagulation parameter
11.adequate renal function
12.age >= 18
13.ability to tolerate proton-pump inhibitors or H2 antagonists during RT
14.women:not pregnant and adequate contraception must be used; men: agree not to father a child during/ within 4 months after trial
15. compliance and geographic proximity to allow proper staging and follow-up
16. phase I only:adequate pancreatic function

Exclusion Criteria

1.previous malignancy within 5 years
2.previous RT to the abdomen or caudal chest
3.TACE, RFA or RT within 8 weeks before registration
4. concurrent treatment with other experimental drugs or other anti-cancer therapy
5.operable disease (curative intent) or planned liver transplantation
6.nutritional intake < 1500 kcal/day
7.weight loss > 15%
8.presence of clinical ascites
9.presence of encephalopathy
10.recent myocard infarction
11.esophageal varices >or = gr 3
12.syptoms of colitis, enteritis, esophagitis, fistula, gastristis, ileus, necrosis, perforation, stricture or ulcer
13.severe anorexia, constipation, dehydration, diarrhea or vomiting
14.any serious underlyuing condition which could impair teh ability of the patient to participate in the trial
15.concommitant treatment with steroids or NSAIDs durinng RT
16.psychiatric disorder precluding understanding of information on trial related topics or giving informed consent

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint of phase I<br /><br>• Dose limiting toxicity (DLT) of RT<br /><br><br /><br>Primary endpoint of phase II<br /><br>• Best objective response of target liver lesions according to RECIST</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints of phase I<br /><br>• Best objective response of target liver lesions according to RECIST<br /><br>• Adverse events (AEs)<br /><br><br /><br>Secondary endpoints of phase II<br /><br>• Volumetric response of target liver lesions at 5 months<br /><br>• Time to progression of target liver lesions<br /><br>• Duration of response of target liver lesions<br /><br>• Stable disease of target liver lesions<br /><br>• Time to liver event<br /><br>• Progression-free survival (PFS)<br /><br>• Overall survival (OS)<br /><br>• Compensatory liver tissue hypertrophy<br /><br>• Child-Pugh Score<br /><br>• Adverse events (AEs)<br /><br>• Serum alpha fetoprotein (AFP) level</p><br>