Trial | NCT00941967  Report issue

Title

Sorafenib With or Without Gemcitabine and Oxaliplatin in Treating Patients With Locally Advanced, Unresectable, or Metastatic Liver Cancer
Randomized Phase II Trial Assessing the Combination of Nexavar® (Sorafenib), and Gemcitabine/Oxaliplatin in Patients Treated for Advanced (Unresectable/Metastatic) Hepatocellular Carcinoma.

  • Phase

    Phase 2

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    78
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.
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.
Study Started
Dec 31
2008
Primary Completion
Dec 31
2010
Study Completion
Dec 31
2012
Last Update
Jul 10
2019

Drug gemcitabine hydrochloride

Given IV

Drug oxaliplatin

Given IV

Drug sorafenib tosylate

Given orally.

Arm I Experimental

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 Experimental

Patients receive oral sorafenib tosylate twice daily on days 1-14.

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
No Results Posted