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Randomized Phase II Trial Assessing the Combination of Nexavar® (Sorafenib), and Gemcitabine/Oxaliplatin in Patients Treated for Advanced (Unresectable/Metastatic) Hepatocellular Carcinoma.

Phase 2
18 Years
Open (Enrolling)
Liver Cancer

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Trial Information

Randomized Phase II Trial Assessing the Combination of Nexavar® (Sorafenib), and Gemcitabine/Oxaliplatin in Patients Treated for Advanced (Unresectable/Metastatic) Hepatocellular Carcinoma.



- 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.


- 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.

Inclusion Criteria


- 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

- No presence of bone metastasis only

- No known brain metastasis


- 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

- 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


- 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

- No other concurrent experimental drugs or anticancer therapy

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Tumor response according to RECIST criteria

Safety Issue:


Principal Investigator

Eric Assenat, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hopital Saint Eloi



Study ID:




Start Date:

December 2008

Completion Date:

Related Keywords:

  • Liver Cancer
  • adult primary hepatocellular carcinoma
  • localized unresectable adult primary liver cancer
  • recurrent adult primary liver cancer
  • advanced adult primary liver cancer
  • Liver Neoplasms
  • Carcinoma, Hepatocellular