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

Liver Cancer Clinical Trial

Official title:

Phase II and Pharmacokinetic Trial of Rebeccamycin Analog in Hepatobiliary Cancers

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00005997
• Other study ID #: CWRU2299
• Secondary ID: U01CA063200P30CA
• Status: Terminated
• Phase: Phase 2
• First received: July 5, 2000
• Last updated: June 9, 2010
• Start date: April 1999
• Est. completion date: November 2005

Study information

• Verified date: June 2010
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: November 2005
• Est. primary completion date: April 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Cholangiocarcinoma
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms
• Liver Cancer
• Liver Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Dowlati A, Posey J, Ramanathan RK, et al.: Multicenter phase II and pharmacokinetic study of rebeccamycin analogue (RA) in advanced biliary cancers. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1070, 2003.

Dowlati A, Posey J, Ramanathan RK, Rath L, Fu P, Chak A, Krishnamurthi S, Brell J, Ingalls S, Hoppel CL, Ivy P, Remick SC. Phase II and pharmacokinetic trial of rebeccamycin analog in advanced biliary cancers. Cancer Chemother Pharmacol. 2009 Dec;65(1):73 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the response rate in patients with advanced hepatobiliary carcinoma treated with rebeccamycin analogue.		Patients are followed every 3 months.	No
Secondary	Assess the toxicity associated with this drug in this patient population.		Patients are followed every 3 months.	Yes