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

September 12, 2008 updated by: The University of Hong Kong

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Hong Kong, China
        • Recruiting
        • Queen Mary Hospital
        • Contact:
        • Principal Investigator:
          • Ronnie Poon, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: 4 cycles
4 cycles

Secondary Outcome Measures

Outcome Measure
Time Frame
Tumor response rate, overall survival and safety of the regimen in HCC patients
Time Frame: 8 cycles
8 cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Anticipated)

December 1, 2008

Study Completion (Anticipated)

December 1, 2008

Study Registration Dates

First Submitted

September 1, 2008

First Submitted That Met QC Criteria

September 12, 2008

First Posted (Estimate)

September 15, 2008

Study Record Updates

Last Update Posted (Estimate)

September 15, 2008

Last Update Submitted That Met QC Criteria

September 12, 2008

Last Verified

September 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HKU-SRG-P001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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