Proof-of-Concept Phase II Study to Evaluate the Anti-Tumor Activity of Sorafenib Along With Pathological and Molecular Changes in Tumor Samples From Patients With Resectable Hepatocellular Carcinoma
Proof-of-Concept Phase II Study to Evaluate the Anti-Tumor Activity of Sorafenib Along With Pathological and Molecular Changes in Tumor Samples From Patients With Resectable Hepatocellular Carcinoma
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.
PURPOSE: This phase II trial is studying how well sorafenib tosylate works in treating patients with liver cancer that can be removed by surgery.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib tosylate twice daily on days 1-28 in the absence of unacceptable toxicity. Approximately 7 days after completion of sorafenib tosylate therapy, patients undergo liver resection.
Blood and tissue specimens are collected periodically for laboratory and biomarker assessments. Biomarkers include both molecular markers investigating the direct antitumor effects of sorafenib tosylate against cancer cells vs the effects of the drug on angiogenesis.
After completion of study treatment, patients are followed up on day 50 and at 3 months after surgery.
DISEASE CHARACTERISTICS:
Histologically confirmed hepatocellular carcinoma (HCC)
Must be eligible for conservative hepatic resection or liver resection with curative intent
No cirrhosis with Child-Pugh score > 7
Chronic liver disease without liver insufficiency and without portal liver hypertension allowed
No known history or presence of metastatic brain or meningeal tumors
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
Life expectancy ≥ 3 months
WBC > 3,000/µL
ANC > 1,500/µL
Platelet count ≥ 100,000/µL
Hemoglobin ≥ 9 g/dL
Bilirubin < 1.5 times upper normal limit (ULN)
AST and ALT ≤ 5 times UNL
Alkaline phosphatase ≤ 5 times ULN
Serum creatinine < 2 times ULN
PT/INR/PTT < 1.5 times UNL
Amylase and lipase < 1.5 times ULN
Negative pregnancy test
Fertile patients must use effective contraception
Body mass index 18.5-30 kg/m^2 (WHO normal range: 18.5-25 kg/m^2)
Able to swallow oral compound
No criterion for unresectability or medical condition that contraindicates surgical resection
No serious concurrent systemic disorder incompatible with the study, including any of the following:
No prior medical disorder, including any of the following:
No other prior malignancy within the past 5 years, except basal cell or squamous cell skin carcinoma or cured in situ cervical carcinoma
No history or concurrent seizure disorder requiring medications (e.g., antiepileptic drugs)
No history of HIV infection, or chronic hepatitis B or C
No active clinically serious bacterial or fungal infection (i.e., grade 2 CTCAE v. 3)
No condition that is unstable or could jeopardize the safety of the patient and his/her compliance with the study
No substance abuse or medical, psychological, or social condition that could interfere with adherence to the study
No known or suspected allergy to the investigational agent or to any agent given concurrently
No presence of asthenia or rash > CTC grade 1 at enrollment
Must be registered in a national health-care system
PRIOR CONCURRENT THERAPY:
No prior orthotopic liver transplantation
Not a candidate for orthotopic liver transplantation
No prior systemic or loco-regional treatment for HCC
No prior organ allograft
No treatment with any other investigational medicinal product within the past 28 days
No concurrent treatment with full-dose anticoagulants
No concurrent or chronic co-administration of CYP3A4 inducers (e.g., rifampin, Hypericum perforatum, phenytoin, carbamazepine, phenobarbital, or dexamethasone)