Sorafenib With Capecitabine and Oxaliplatin for Advanced or Metastatic Hepatocellular Carcinoma

NCT ID: NCT00752063

Last Updated: 2008-09-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2008-12-31

Brief Summary

HCC is an aggressive, largely chemo-resistant cancer with a poor prognosis, currently there is no effective systemic chemotherapy for HCC. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are both overexpressed in HCC and thought to contribute to tumor development. Oxaliplatin in combination with other chemotherapies or biologic agents have been shown to be an effective and safe treatment in advanced HCC patients.

Sorafenib, an oral multi-kinase inhibitor, blocks tumor cell proliferation by targeting multiple growth factor pathways and also exerts an anti-angiogenic effect. Clinically, single agent Sorafenib has been shown to have some efficacy in patients with advanced HCC and the primary result of prolonged overall survival seems to have been achieved in the phase III trial.

Detailed Description

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with an annual incidence of over 500,000 new patients and more than half of the new cases occur in China. The most common etiological causes of HCC are hepatitis B and hepatitis C viral infections.

HCC is a cancer of high particular relevance in Hong Kong because of the high prevalence (10%) of hepatitis B virus infection in the population. It is the second most common cancer causing death in Hong Kong. Surgical resection and liver transplantation are regarded as the main curative treatments for HCC. Nevertheless, the majority of patients have unresectable HCCs because of advanced tumor stage and poor liver function. Besides, transplantation is indicated only for early small HCCs, and its application is limited by the shortage of liver graft, which is a particularly severe problem in Hong Kong.

HCC is an aggressive, largely chemo-resistant cancer with a poor prognosis, currently there is no effective systemic chemotherapy for HCC. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are both overexpressed in HCC and thought to contribute to tumor development. Oxaliplatin in combination with other chemotherapies or biologic agents have been shown to be an effective and safe treatment in advanced HCC patients. Sorafenib, an oral multi-kinase inhibitor, blocks tumor cell proliferation by targeting multiple growth factor pathways and also exerts an anti-angiogenic effect.

Sorafenib has been approved by FDA for use in renal cell carcinoma based on prolonged survival in phase III trials. Single agent Sorafenib has been shown to have some efficacy in patients with advanced HCC and the primary result of prolonged overall survival have been achieved in a recent randomized phase III trial. However, most patients would only have disease stabilization as the phase II trial only showed a tumor response rate of only 8% (PR & MR). Combination with chemotherapy may improve the tumor response rate.

Conditions

Advanced Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma

Keywords

Sorafenib; Capecitabine; Oxaliplatin; Advanced Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

All subjects will receive Sorafenib with Capecitabine and Oxaliplatin

Group Type: EXPERIMENTAL

Sorafenib with Capecitabine and Oxaliplatin

Intervention Type: DRUG

Regimen 1: Oxaliplatin 85 mg/m2 (50 mg per vial) administered intravenously on day 1 of each cycle Regimen 2: Capecitabine 1700 mg/m2 p.o. (850 mg/m2 BD) day 1 to 7 Regimen 3: Sorafenib 400 mg (200 mg/tablet) orally BD day 1 to 14

Interventions

Sorafenib with Capecitabine and Oxaliplatin

Regimen 1: Oxaliplatin 85 mg/m2 (50 mg per vial) administered intravenously on day 1 of each cycle Regimen 2: Capecitabine 1700 mg/m2 p.o. (850 mg/m2 BD) day 1 to 7 Regimen 3: Sorafenib 400 mg (200 mg/tablet) orally BD day 1 to 14

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with locally advanced or metastatic HCC not suitable surgical or locoregional therapies
• Age more than 18 years
• Performance status 0 or 1
• Life expectancy of 3 months
• Prior radiotherapy more than 3 weeks prior to study entry
• No prior systemic therapy
• Hb more than 8.5 g/dl
• ANC more than 1,500/mm3
• PLT more than 75 x 109/L
• PT-INR/PTT less than 1.5 x upper limit of normal
• Total bilirubin of less than 1.5 x upper limit of normal
• Serum creatinine less than 1.5 x upper limit of normal
• Serum AST and ALT less than 2.5 x upper limit of normal

Exclusion Criteria

• History of cardiac disease
• Symptomatic metastatic brain or meningeal tumors
• Main portal vein tumor thrombosis
• Ascites uncontrolled by medication
• Variceal or gastrointestinal bleeding within three months prior to start of treatment
• Seizure disorder requiring medication
• Patients undergoing renal dialysis
• Previous or concurrent cancer that is distinct in primary site
• Prior use of any systemic anti-cancer treatment
• Prior use of Raf-kinase inhibitors (RKI), VEGF inhibitors, MEK inhibitors or Farnesyl transferase inhibitors
• Patients on any local ablative treatment or TACE within 6 weeks
• Radiotherapy during study or within 3 weeks
• Major surgery within 4 weeks
• Concomitant treatment of rifampin or St John's Wort
• Pregnant or breast-feeding patients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

The University of Hong Kong,

Locations

Queen Mary Hospital

Hong Kong, , China

Site Status: RECRUITING

Countries

China

Facility Contacts

Ida Choi, MPhil

Role: primary

Other Identifiers

HKU-SRG-P001

Identifier Type: -

Identifier Source: org_study_id