Temsirolimus in Treating Patients With Advanced Liver Cancer and Cirrhosis

Federation Francophone de Cancerologie Digestive

Status and phase

Terminated

Phase 2

Conditions

Liver Cancer

Treatments

Drug: temsirolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT01079767

EUDRACT-2009-014443-36

EU-21004

CDR0000666229

FFCD-0903

Details and patient eligibility

About

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.

Full 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.

Enrollment

6 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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