SECOX: Sorafenib With Capecitabine and Oxaliplatin for Advanced or Metastatic Hepatocellular Carcinoma

Sponsor

The University of Hong Kong (Other)

Overall Status

Unknown status

CT.gov ID

NCT00752063

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma Metastatic Hepatocellular Carcinoma	Drug: Sorafenib with Capecitabine and Oxaliplatin	Phase 2

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase IIa Trial of Sorafenib With Capecitabine and Oxaliplatin in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma

Study Start Date :

Sep 1, 2007

Anticipated Primary Completion Date :

Dec 1, 2008

Anticipated Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A All subjects will receive Sorafenib with Capecitabine and Oxaliplatin	Drug: 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

Arm

Intervention/Treatment

Experimental: A

All subjects will receive Sorafenib with Capecitabine and Oxaliplatin

Drug: 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

Outcome Measures

Primary Outcome Measures

Progression-free survival [4 cycles]

Secondary Outcome Measures

Tumor response rate, overall survival and safety of the regimen in HCC patients [8 cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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