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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II and Pharmacokinetic Trial of Rebeccamycin Analog in Hepatobiliary Cancers

Conditions
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Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Liver Cancer

Intervention / Treatment
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* Drug: becatecarin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: becatecarin|Cohorts of 3-6 patients receive escalating doses of rebeccamycin analogue until the maximum tolerated dose (MTD) is determined.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the response rate in patients with advanced hepatobiliary carcinoma treated with rebeccamycin analogue. |  | Patients are followed every 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the toxicity associated with this drug in this patient population. |  | Patients are followed every 3 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized unresectable adult primary liver cancer, advanced adult primary liver cancer, unresectable gallbladder cancer, unresectable extrahepatic bile duct cancer, adult primary hepatocellular carcinoma, cholangiocarcinoma of the gallbladder, cholangiocarcinoma of the extrahepatic bile duct, adult primary cholangiocellular carcinoma