RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of rebeccamycin analogue in treating patients who have advanced liver and/or biliary cancer.

Condition	Treatment or Intervention	Phase
adult primary liver cancer cholangiocarcinoma of the extrahepatic bile duct cholangiocarcinoma of the gallbladder unresectable extrahepatic bile duct cancer unresectable gallbladder cancer	Drug: rebeccamycin analogue  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response rate in patients with advanced hepatobiliary carcinoma treated with rebeccamycin analogue.
• Assess the toxicity associated with this drug in this patient population.
• Evaluate the survival of this patient population treated with this drug.
• Determine the pharmacokinetics of this drug in this patient population.

OUTLINE: This is a partial dose-escalation study.

Patients receive rebeccamycin analogue IV over 1 hour daily on days 1-5. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are assigned to 1 of 2 cohorts according to hepatic dysfunction. (Cohort I closed to accrual as of 11/1/03.)

• Cohort I (closed to accrual as of 11/1/03): Patients receive a fixed dose of rebeccamycin analogue.
• Cohort II: Cohorts of 3-6 patients receive escalating doses of rebeccamycin analogue until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 6-37 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of advanced hepatobiliary carcinoma not amenable to conventional surgery
• Gall bladder carcinoma
• Cholangiocarcinoma
• Carcinoma of the ampulla
• Hepatocellular carcinoma (eligible for cohort II only)
• Measurable disease
• No known brain metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 10 g/dL

Hepatic:

• Bilirubin less than 3 mg/dL
• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 2.5 times upper limit of normal (ULN)
• Bilirubin greater than 1.5 mg/dL and less than 3 mg/dL OR
• Bilirubin no greater 1.5 mg/dL AND AST greater than 2.5 times ULN

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for cholangiocarcinoma or hepatobiliary carcinoma

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No concurrent combination antiviral therapy for HIV-positive patients

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States; Recruiting
New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10461,  United States; Recruiting
Ohio
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting

Study chairs or principal investigators

Afshin Dowlati, MD,  Study Chair,  Ireland Cancer Center   

Study ID Numbers:  CDR0000068001; CWRU-2299; NCI-96; NCT00005997
Record last reviewed:  December 2003
Last Updated:  April 4, 2005
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00005997
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08