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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00471484
First received: May 8, 2007
Last updated: June 21, 2011
Last verified: November 2008
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Biological: recombinant interferon alfa-2b
Drug: doxorubicin hydrochloride
Drug: fluorouracil
Drug: oxaliplatin
Other: diagnostic laboratory biomarker analysis
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Procedure: adjuvant therapy
Procedure: biopsy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective tumor response rate as measured by RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum VEGF levels [ Designated as safety issue: No ]
  • Tissue VEGF expression [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: March 2007
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.

  Eligibility

Ages Eligible for Study:   16 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471484

Locations
Singapore
National Cancer Centre - Singapore Recruiting
Singapore, Singapore, 169610
Contact: Donald Poon, MD    65-6-436-8000      
Sponsors and Collaborators
National Cancer Centre, Singapore
Investigators
Study Chair: Donald Poon, MD National Cancer Centre, Singapore
Investigator: Kian Fong Foo, MD National Cancer Centre, Singapore
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00471484     History of Changes
Other Study ID Numbers: CDR0000543536, SINGAPORE-OC-GI-01-06, SINGAPORE-IRB-06-16-HEP, SINGAPORE-CTC0600327, SPRI-SINGAPORE-OC-GI-01-06
Study First Received: May 8, 2007
Last Updated: June 21, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
childhood hepatocellular carcinoma
stage III childhood liver cancer
stage IV childhood liver cancer

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fluorouracil
Oxaliplatin
Liposomal doxorubicin
Interferons
Doxorubicin
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014