Sorafenib Tosylate With or Without Gemcitabine Hydrochloride and Oxaliplatin in Treating Patients With Locally Advanced, Unresectable, or Metastatic Liver Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00941967
First received: July 17, 2009
Last updated: April 7, 2010
Last verified: July 2009
  Purpose

RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether sorafenib tosylate is more effective when given with or without gemcitabine hydrochloride and oxaliplatin in treating patients with liver cancer.

PURPOSE: This randomized phase II trial is studying sorafenib tosylate to see how well it works when given with or without gemcitabine hydrochloride and oxaliplatin in treating patients with locally advanced, unresectable, or metastatic liver cancer.


Condition Intervention Phase
Liver Cancer
Drug: gemcitabine hydrochloride
Drug: oxaliplatin
Drug: sorafenib tosylate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial Assessing the Combination of Nexavar® (Sorafenib), and Gemcitabine/Oxaliplatin in Patients Treated for Advanced (Unresectable/Metastatic) Hepatocellular Carcinoma.

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response according to RECIST criteria [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 78
Study Start Date: December 2008
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral sorafenib tosylate as in arm I. Patients also receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment with gemcitabine hydrochloride and oxaliplatin repeats every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
Given orally.
Experimental: Arm II
Patients receive oral sorafenib tosylate twice daily on days 1-14.
Drug: gemcitabine hydrochloride
Given IV
Drug: oxaliplatin
Given IV
Drug: sorafenib tosylate
Given orally.

Detailed Description:

OBJECTIVES:

Primary

  • Assess progression-free survival (RECIST) in patients with locally advanced, unresectable or metastatic hepatocellular carcinoma treated with sorafenib tosylate with vs without gemcitabine hydrochloride and oxaliplatin.

Secondary

  • Evaluate the tolerability of these regimens in these patients.
  • Determine the objective response rate (RECIST) in patients treated with these regimens.
  • Assess the overall survival of patients treated with these regimens.
  • Evaluate the pharmacokinetics of sorafenib tosylate.
  • Assess biomarkers (e.g., pERK levels) associated with treatment response.
  • Assess angiogenic response by functional imaging.

OUTLINE: This is a multicenter study. Patients are stratified according to performance status and CLIP score. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral sorafenib tosylate as in arm I. Patients also receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment with gemcitabine hydrochloride and oxaliplatin repeats every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-14. In both arms, courses with sorafenib tosylate repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Blood samples and/ or tumor tissue samples may be collected for further analysis.

After completion of study therapy, patients are followed every 2 months until disease progression and then every 6 months thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed hepatocellular carcinoma not amenable to liver transplantation

    • Locally advanced, unresectable, or metastatic disease
  • At least 1 lesion accurately measured in ≥ 1 dimension according to RECIST criteria AND has not been previously treated with local therapy (e.g., intra-arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation)

    • No presence of bone metastasis only
  • No known brain metastasis

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Life expectancy > 12 weeks
  • ANC > 1,500/mm^3
  • WBC > 3,000/mm^3
  • Platelet count ≥ 90,000/mm^3
  • Hemoglobin > 10 g/dL
  • Total protein ≥ 40%
  • ALT or AST ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • Amylase and lipase < 1.5 times ULN
  • Creatinine < 1.5 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • Albumin ≥ 2.8 mg/dL
  • INR ≤ 2.3
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during study and for up to 4 months for females and 6 months for males after completion of study treatment
  • CLIP score 0-3
  • No Child Pugh score B or C cirrhosis
  • No known HIV positivity
  • No other prior malignancy, except adequately treated or curative basal cell skin cancer or carcinoma in situ of the cervix
  • No known or suspected allergy to the investigational agent or any agent given in association with this study
  • No cardiovascular disease, including any of the following:

    • Cardiac arrhythmia requiring antiarrhythmic therapy, except beta-blockers or digoxin for chronic atrial fibrillation
    • Active coronary artery disease or ischemia
    • Myocardial infarction within the past 6 months
    • NYHA class II-IV congestive heart failure
  • No uncontrolled hypertension
  • No severe active bacterial or fungal infection > CTCAE v3.0 grade 2
  • No peripheral neuropathy ≥ grade 2
  • No condition that could affect the absorption of study drug, including any of the following:

    • Malabsorption syndrome
    • Disease significantly affecting gastrointestinal function
    • Bowel obstruction or sub-obstruction
  • No dysphagia or inability to swallow tablets
  • No history of seizures requiring long-term antiepileptic treatment
  • No unstable condition that would jeopardize safety or compliance with study including any of the following :

    • Medical, psychological, or social conditions
    • Substance abuse
    • Legal incapacity or limited legal capacity
  • No psychological, familial, social, or geographic reasons that would preclude clinical follow-up
  • Must be registered in a social security program

PRIOR CONCURRENT THERAPY:

  • No prior organ transplantation with immunosuppressive treatment
  • No prior systemic chemotherapy or systemic antiangiogenic treatment for hepatocellular carcinoma
  • No prior major resection of the stomach or proximal small bowel
  • Prior anticoagulation therapy (e.g., warfarin or heparin) allowed with INR parameters within normal limit range
  • At least 4 weeks since prior local therapy to lesions and treated lesions may not be selected as target lesions
  • No concurrent or prior long-term treatment with CYP3A4 inducers (e.g., rifampin, hypericum perforatum, phenytoin, carbamazepine, phenobarbital, and dexamethasone)
  • No concurrent antitumoral treatment, including tamoxifen, interferon, or somatostatin analogues
  • No other concurrent experimental drugs or anticancer therapy
  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: NCT00941967

Locations
France
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle Recruiting
Montpellier, France, 34295
Contact: Eric Assenat, MD    33-4-6761-2593      
Sponsors and Collaborators
Centre Val d'Aurelle - Paul Lamarque
Investigators
Principal Investigator: Eric Assenat, MD Hopital Saint Eloi
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00941967     History of Changes
Other Study ID Numbers: CDR0000638394, CLCC-GONEXT-PRODIGE-10, VA 2007/40, INCA-RECF0917, EUDRACT-2008-000123-26
Study First Received: July 17, 2009
Last Updated: April 7, 2010
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
advanced adult primary liver cancer

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gemcitabine
Sorafenib
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014