RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill liver cancer cells. PURPOSE: Phase II trial to study the effectiveness of doxorubicin and interleukin- 2 in treating patients who have liver cancer that cannot be removed by surgery.

Condition	Treatment or Intervention	Phase
recurrent adult primary liver cancer adult primary hepatocellular carcinoma localized unresectable adult primary liver cancer	Drug: doxorubicin  Drug: interleukin-2	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the immunological response to doxorubicin and protracted recombinant interleukin-2 in terms of alterations in hepatocellular carcinoma specific cytotoxic T cells detectable in peripheral blood in patients with unresectable hepatocellular carcinoma. II. Determine the toxicity of this treatment regimen in this patient population. III. Determine the tumor response to this regimen in terms of changes in alpha fetoprotein and tumor size measured by CT scan in these patients. IV. Determine the progression free survival and overall survival of this patient population treated with this regimen. V. Determine the correlation between immunological response, tumor response, progression free survival and overall survival in these patients.

PROTOCOL OUTLINE: Patients receive doxorubicin IV over 3-5 minutes on day 1 and recombinant interleukin-2 (IL-2) IV continuously beginning on day 5 and continuing until day 57. Patients achieving partial or complete clinical response regardless of immunological response and patients with stable disease and an immunological response continue on IL-2 therapy continuously until day 92. Patients with stable disease and no immunological response receive an additional dose of doxorubicin on day 57 and then continue on IL-2 until day 92. Patients who are clinically eligible with progressive disease and an immunological response continue IL-2 therapy as above. Patients are followed at 2 weeks and then monthly thereafter.

PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within approximately 3 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven hepatocellular carcinoma OR Elevation of alpha fetoprotein (AFP) (greater than 400 ng/mL) in the presence of a space occupying lesion in the liver with known chronic liver disease; Lesion must be easily biopsied
• Unresectable disease
• Bidimensionally measurable disease by radiography OR Evaluable disease with elevated AFP; Okuda stage I disease; Tumor size less than 50% of liver; No ascites; Albumin greater than 3 g/dL; Bilirubin less than 2 mg/dL OR Okuda stage II disease; Bilirubin as in stage I; If ascites present, albumin must be greater than 3 g/dL

--Prior/Concurrent Therapy--

• Biologic therapy: At least 6 weeks since prior immunotherapy, including interferon
• Chemotherapy: No prior systemic or intra arterial doxorubicin; At least 6 weeks since prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: See Disease Characteristics
• Other: At least 4 weeks since prior investigational therapy

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: Hemoglobin at least 9.0 g/dL; Neutrophil count at least 1,500/mm3; Platelet count at least 80,000/mm3
• Hepatic: See Disease Characteristics; SGOT/SGPT no greater than 4 times upper limit of normal; Any cause of underlying liver disease including hepatitis B or C allowed
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: No poor cardiac function; No myocardial infarction within the past 6 months; No poorly controlled arrhythmia; No congestive heart failure; LVEF at least 45% by MUGA
• Other: No active hepatic encephalopathy; No other active malignancies except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix; HIV negative; No immunodeficiency; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

New York
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States

Study chairs or principal investigators

Lawrence P. Leichman,  Study Chair,  Roswell Park Cancer Institute   

Study ID Numbers:  CDR0000067494; RPCI-RP-9814; NCI-G99-1663
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004248
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08