radiation therapy in treating patients with liver cancer that cannot be removed by surgery

Conditions: Liver Cancer

Summary: rationale: radiation therapy uses high-energy x-rays to kill tumor cells. this may be an effective treatment for liver cancer. purpose: this phase i/ii trial is studying the side effects and best dose of external-beam radiation therapy in treating patients with liver cancer that cannot be removed by surgery.

objectives: * to assess the feasibility and safety of radiotherapy (rt) in patients with hepatocellular carcinoma. (phase i) * to assess the safety and efficacy of rt in these patients. (phase ii) * to generate reproducible peptide patterns of the serum proteome or specific serum sub proteomes in these patients. * to assess changes in the proteome or sub proteome patterns after rt in these patients. * to detect peptides that discriminate between before and after rt in these patients. * to identify these discriminating peptides in these patients. outline: this is a multicenter, phase i dose-escalation study followed by a phase ii study. patients undergo radiotherapy (rt) once daily, five days a week, for 6 weeks. intensity-modulated, 3-dimensional conformal, or fractionated stereotactic rt may be used. after completion of study therapy, patients in the phase i portion are followed for 1 year and patients in the phase ii portion are followed for 3 years.

Eligibility criteria:
disease characteristics: * histologically, cytologically, or radiologically confirmed hepatocellular carcinoma * clinical stage t2-4, n0-1, m0 (stage ii, iiia, iiib, iiic) or unresectable t1, n0-1, m0 (stage i) disease * m1 disease allowed in phase i if at least 90% of the tumor load (volume) is in the liver * measurable disease (at least one liver lesion that can be measured in at least one dimension as ≥ 10 mm in multislice ct scan/mri) * volumetry of liver tumor and residual liver tissue: residual liver volume (= total liver volume - gross tumor volume) has to be ≥ 800 ml and ≥ 40% of total liver volume * no operable disease (with curative intent or planned liver transplantation) * no presence of clinical ascites patient characteristics: * who performance status 0-2 * cirrhosis child-pugh class a or b (child-pugh score of ≤ 9) * hemoglobin ≥ 100 g/l * anc ≥ 1,200/mm³ * platelet count ≥ 50,000/mm³ * alt and ast ≤ 7 times upper limit of normal (uln) * ap ≤ 10 times uln * bilirubin ≤ 50 μmol/l * inr ≤ 2 * creatinine clearance ≥ 50 ml/min * functional left kidney (scintigraphy mandatory for phase i, phase ii only if indicated) * lipase ≤ 2 times uln (phase i only) * able to tolerate proton-pump inhibitors or h2 antagonists during radiation therapy * not pregnant * negative pregnancy test * fertile patients must use effective contraception during and for 4 months after completion of study therapy * no prior malignancy allowed, except for the following: * adequately treated cervical carcinoma in situ * adequately treated localized nonmelanoma skin cancer * any other malignancy from which patient has been disease-free for 5 years * no presence of medically uncontrolled encephalopathy * no myocardial infarction within the past 6 months * no esophageal varices ≥ grade 3, with red signs, or bleeding within the past 3 months * no symptoms of colitis, enteritis, esophagitis, fistula, gastritis, ileus, necrosis, perforation, stricture, or ulcer * no severe anorexia, constipation, dehydration, diarrhea, or vomiting * no serious underlying medical condition that, in the opinion in the investigator, would preclude study participation (e.g., active autoimmune disease or uncontrolled diabetes) * portal vein thrombosis allowed * no psychiatric disorder precluding understanding of information on study related topics or giving informed consent * no nutritional intake \< 1500 calories per day (corrected) * no weight loss ≥ 15 % within the past 3 months prior concurrent therapy: * at least 8 weeks since prior transarterial chemoembolization (tace), radiofrequency ablation, or radiotherapy (rt) unless progressive disease was documented after this therapy * at least 21 days since prior and no other concurrent treatment with experimental drugs * at least 21 days since prior and no other concurrent treatment on another clinical trial * at least 21 days since prior and no other concurrent anticancer therapy * no prior rt to the abdomen or caudal chest * prior rt to pelvis allowed * prior rt to chest must be above d5 vertebra * portal vein embolization ligation or pre-rt tace allowed * no concurrent treatment with steroids or non-steroidal anti-inflammatory drugs during rt (proton-pump inhibitor allowed)

Keywords: advanced adult primary liver cancer localized unresectable adult primary liver cancer adult primary hepatocellular carcinoma