Temsirolimus in Treating Patients With Advanced Liver Cancer and Cirrhosis

This study has been terminated.
(The study treminated early according to DSMB recommendantions)
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT01079767
First received: March 2, 2010
Last updated: March 3, 2014
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Advanced Hepatocellular Carcinoma on Child B Cirrhosis: Tolerance and Efficacy of Torisel® (Temsirolimus)

Resource links provided by NLM:


Further study details as provided by Federation Francophone de Cancerologie Digestive:

Primary Outcome Measures:
  • 3-month disease-control rate according to RECIST criteria [ Time Frame: 2010 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 3-month objective response rate according to RECIST criteria [ Time Frame: 2010 ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: January 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Temsirolimus
Temsirolimus
Drug: temsirolimus

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01079767

Locations
France
Centre Hospitalier Universitaire Henri Mondor
Creteil, France, 94010
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
Principal Investigator: Thomas Decaens, MD Centre Hospitalier Universitaire Henri Mondor
Principal Investigator: Christophe Duvoux Centre Hospitalier Universitaire Henri Mondor
  More Information

Additional Information:
No publications provided

Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT01079767     History of Changes
Other Study ID Numbers: CDR0000666229, FFCD-0903, EUDRACT-2009-014443-36, EU-21004
Study First Received: March 2, 2010
Last Updated: March 3, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Federation Francophone de Cancerologie Digestive:
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014