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

NCT ID: NCT00471484

Last Updated: 2011-06-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31

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.

Conditions

Liver Cancer

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

recombinant interferon alfa-2b

Intervention Type: BIOLOGICAL

doxorubicin hydrochloride

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

diagnostic laboratory biomarker analysis

Intervention Type: OTHER

immunoenzyme technique

Intervention Type: OTHER

immunohistochemistry staining method

Intervention Type: OTHER

adjuvant therapy

Intervention Type: PROCEDURE

biopsy

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

PRIOR CONCURRENT THERAPY:

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Centre, Singapore

OTHER

Sponsor Role: lead

Principal Investigators

Donald Poon, MD

Role: STUDY_CHAIR

National Cancer Centre, Singapore

Kian Fong Foo, MD

Role:

National Cancer Centre, Singapore

Locations

National Cancer Centre - Singapore

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Facility Contacts

Donald Poon, MD

Role: primary

65-6-436-8000

References

Ang MK, Poon D, Foo KF, Chung YF, Chow P, Wan WK, Thng CH, Ooi L. A new chemoimmunotherapy regimen (OXAFI) for advanced hepatocellular carcinoma. Hematol Oncol Stem Cell Ther. 2008 Jul-Sep;1(3):159-65. doi: 10.1016/s1658-3876(08)50024-0.

Reference Type: RESULT

PMID: 20063546 (View on PubMed)

Other Identifiers

SINGAPORE-OC-GI-01-06

Identifier Type: -

Identifier Source: secondary_id

SINGAPORE-IRB-06-16-HEP

Identifier Type: -

Identifier Source: secondary_id

SINGAPORE-CTC0600327

Identifier Type: -

Identifier Source: secondary_id

SPRI-SINGAPORE-OC-GI-01-06

Identifier Type: -

Identifier Source: secondary_id

CDR0000543536

Identifier Type: -

Identifier Source: org_study_id