temsirolimus in treating patients with advanced liver cancer and cirrhosis

Conditions: Liver Cancer

Summary: rationale: temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. purpose: this phase ii trial is studying how well temsirolimus works in treating patients with advanced liver cancer and cirrhosis.

objectives: primary * to determine the 3-month disease-control rate according to recist criteria in patients with advanced hepatocellular carcinoma and child-pugh class b cirrhosis. secondary * to determine the 3-month objective response rate according to recist criteria in these patients. * to determine the 1-month metabolic response rate on pet/ct scan in these patients. * to determine the 1-month perfusion response rate on hepatic perfusion ct scan in these patients. * to determine the time to progression in patients treated with this drug. * to determine the progression-free survival of patients treated with this drug. * to determine the overall survival of patients treated with this drug. * to assess quality of life according to qlq-c30 and qlq-hcc18 questionnaires. * to determine the clinical and biological tolerance of this drug in these patients. * to determine the rate of m-tor pathway activation and vegf level. * to evaluate the pharmacokinetics of this drug in select patients. outline: this is a multicenter study. patients receive temsirolimus iv over 30-60 minutes on day 1. treatment repeats once a week in the absence of disease progression or unacceptable toxicity. patients also undergo fludeoxyglucose f 18 (fdg) positron emission tomography/computed tomography (pet/ct) scan and perfusion ct scan of the liver at baseline and periodically during study treatment. patients complete quality of life questionnaires (qlc-c30 and qlq-hcc18) periodically. some patients undergo blood and tissue sample collection periodically for pharmacological and laboratory studies. after completion of study therapy, patients are followed for up to 24 months.

Eligibility criteria:
disease characteristics: * diagnosis of hepatocellular carcinoma (hcc) according to the european association for the study of the liver (easl) criteria * advanced disease * must be morphologically evaluable * hcc not accessible to other treatment (e.g., surgery, radiofrequency, or chemoembolization) and can not benefit from antiangiogenic therapy * clip score ≤ 3 (except for patients with tumors invading more than 50% of tumor volume) * child-pugh cirrhosis score between b7 and b9, meeting the following criteria: * diagnosed clinically, biologically (e.g., prothrombin time, platelets, or albumin), endoscopically (signs of portal hypertension) and morphologically (dysmorphic liver on ultrasound or ct scan), or by liver biopsy * not a candidate for transplantation and has not received a liver transplant patient characteristics: * ecog performance status 0-2 * life expectancy ≥ 3 months * platelet count ≥ 50,000/mm\^3 * neutrophil count ≥ 1,500/mm\^3 * creatinine clearance ≥ 60 ml/min * gfr ≥ 30 ml/min * serum cholesterol ≤ 350 mg/dl * triglycerides ≤ 300 mg/dl * not pregnant or nursing * fertile patients must use effective contraception during and for more than 2 months after completion of study therapy * no history of other cancer on treatment * no cardiopulmonary disease impairment, including a history of stable or unstable angina or myocardial infarction * no active infection except for viral hepatitis * no hiv positivity prior concurrent therapy: * see disease characteristics * at least 2 weeks since prior inhibitors or inducers of p-glycoprotein, cyp3a4, or cyp3a5 * at least 4 weeks since prior surgery, radiotherapy (except radiotherapy to the bone), transarterial chemoembolization, immunotherapy, or other investigational drug for hcc * at least 6 months since prior chemotherapy

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