Temsirolimus in Treating Patients With Advanced Liver Cancer and Cirrhosis

NCT ID: NCT01079767

Last Updated: 2014-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31

Brief 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.

Detailed Description

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.

Conditions

Liver Cancer

Study Design

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

Study Groups

Temsirolimus

Temsirolimus

Group Type: OTHER

temsirolimus

Intervention Type: DRUG

Interventions

temsirolimus

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

Sponsors

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Decaens, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Henri Mondor

Christophe Duvoux

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Henri Mondor

Locations

Centre Hospitalier Universitaire Henri Mondor

Créteil, , France

Countries

France

Other Identifiers

FFCD-0903

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2009-014443-36

Identifier Type: -

Identifier Source: secondary_id

EU-21004

Identifier Type: -

Identifier Source: secondary_id

CDR0000666229

Identifier Type: -

Identifier Source: org_study_id