Rebeccamycin Analogue in Treating Patients With Advanced Liver and/or Biliary Cancer

Phase II and Pharmacokinetic Trial of Rebeccamycin Analog in Hepatobiliary Cancers

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.

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.

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

  • Cohort I (closed to accrual as of 11/1/03)

    • Bilirubin no greater than 1.5 mg/dL
    • AST no greater than 2.5 times upper limit of normal (ULN)

  • Cohort II

    • 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