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

Phase 2
Conditions
Liver Cancer
Registration Number
NCT00471484
Lead Sponsor
National Cancer Centre, Singapore
Brief Summary

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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
54
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Objective tumor response rate as measured by RECIST criteria
Secondary Outcome Measures
NameTimeMethod
Serum VEGF levels
Tissue VEGF expression

Trial Locations

Locations (1)

National Cancer Centre - Singapore

🇸🇬

Singapore, Singapore

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