Combination Chemotherapy and Interferon Alfa-2b in Treating Patients With Nonmetastatic Liver Cancer That Cannot Be Removed by Surgery

June 21, 2011 updated by: National Cancer Centre, Singapore

A Phase II Trial of Oxaliplatin/Adriamycin/5 Fluorouracil in Continuous Infusion / Interferon α-2b (OXAFI) Combination as Neoadjuvant Therapy in Unresectable Non-Metastatic Hepatocellular Carcinoma

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, doxorubicin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Interferon alfa may interfere with the growth of tumor cells. Giving combination chemotherapy together with interferon alfa may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with interferon alfa-2b works in treating patients with nonmetastatic liver cancer that cannot be removed by surgery.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the response rate in patients with unresectable, nonmetastatic hepatocellular carcinoma treated with neoadjuvant oxaliplatin, doxorubicin hydrochloride, fluorouracil, and recombinant interferon alfa-2b.

Secondary

  • Determine the overall survival of patients treated with this regimen.
  • Determine the progression-free survival of patients treated with this regimen.
  • Determine the rate of conversion to resectability of tumor in patients treated with this regimen.
  • Determine the toxicity profile of this regimen in these patients.
  • Assess the quality of life of patients treated with this regimen.
  • Correlate changes in serological markers of angiogenesis before and after treatment with clinical outcome in these patients.
  • Correlate and validate the use of functional imaging before and after treatment with clinical outcome in these patients.

OUTLINE: Patients receive neoadjuvant OXAFI therapy comprising oxaliplatin IV and doxorubicin hydrochloride IV on days 1, 8 and 15; fluorouracil IV continuously on days 1-28; and recombinant interferon alfa-2b subcutaneously three times weekly in weeks 1-4. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive at least 2 courses of neoadjuvant therapy before undergoing evaluation for response. Patients whose disease becomes resectable after achieving a complete or partial response proceed to surgery. Patients whose disease remains unresectable are reevaluated until their disease either becomes resectable, they complete neoadjuvant therapy, or they meet discontinuation criteria.

At least 2 weeks after receiving neoadjuvant therapy, patients whose disease is resectable undergo surgery for potentially complete resection of their tumors with curative intent. Patients who achieve complete resection proceed to adjuvant therapy.

At least 4 weeks after surgery, patients may restart OXAFI as adjuvant therapy, provided they have fully recovered from surgery and have received fewer than 6 courses of neoadjuvant therapy. Adjuvant therapy repeats every 28 days for a total of 6 courses (including neoadjuvant OXAFI) in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and tissue collection at baseline and periodically during study for evaluation of circulating and tissue biomarkers of angiogenesis. Serum from venous blood samples is analyzed for concentration of VEGF by ELISA. Tumor tissue obtained before and after treatment is examined for tumor VEGF expression, microvessel density, and cellular proliferation by IHC.

Patients complete quality of life questionnaires at baseline, monthly during study treatment, after course 6 of neoadjuvant chemotherapy, or upon discontinuation of study treatment.

Patients are followed periodically for up to 5 years after curative resection of their tumors.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

54

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

  • Singapore
      • Singapore, Singapore, 169610
        • Recruiting
        • National Cancer Centre - Singapore
        • Contact:
          • Donald Poon, MD
          • Phone Number: 65-6-436-8000

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

16 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed hepatocellular carcinoma

    • Advanced, unresectable, nonmetastatic disease
    • Multifocal disease within the same lobe of the liver allowed
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
  • No intractable ascites that cannot be controlled by medical therapy
  • No extrahepatic metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 3 months
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 2.9 mg/dL
  • AST and ALT ≤ 5 times upper reference range (URR)
  • Albumin > 30 g/L
  • Creatinine ≤ 1.5 times URR
  • Creatinine clearance > 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study therapy
  • No other prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No concurrent substantial medical illness, such as cardiac or renal disease
  • MUGA heart study normal
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition used in the study
  • No history of autoimmune disease
  • No thyroid dysfunction
  • No active hepatitis B or C flare or chronic active hepatitis

  • Hepatitis B surface antigen (HBsAg) status known

    • If HBsAg is negative, anti-HBc antibodies should be tested; if anti-HBc is positive, then hepatitis B virus (HBV) DNA detection should be performed to discern presence of mutant HBV carriage
  • No alcohol or drug abuse

  • No concurrent uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia

  • No psychiatric illness or social situation that would preclude study compliance

    • Patients with a history of depression or psychiatric disorders are ineligible

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy and/or radiotherapy
  • No other concurrent investigational agents

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
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective tumor response rate as measured by RECIST criteria

Secondary Outcome Measures

Outcome Measure
Serum VEGF levels
Tissue VEGF expression

Collaborators and Investigators

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

Sponsor

National Cancer Centre, Singapore

Investigators

  • Study Chair: Donald Poon, MD, National Cancer Centre, Singapore
  • Kian Fong Foo, MD, National Cancer Centre, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

March 1, 2007

Study Registration Dates

First Submitted

May 8, 2007

First Submitted That Met QC Criteria

May 8, 2007

First Posted (Estimate)

May 10, 2007

Study Record Updates

Last Update Posted (Estimate)

June 22, 2011

Last Update Submitted That Met QC Criteria

June 21, 2011

Last Verified

November 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000543536
  • SINGAPORE-OC-GI-01-06
  • SINGAPORE-IRB-06-16-HEP
  • SINGAPORE-CTC0600327
  • SPRI-SINGAPORE-OC-GI-01-06

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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