Clinical trial NCT00005997: Rebeccamycin Analogue in Treating Patients With Advanced Liver and/or Biliary Cancer
Official title: Phase II and Pharmacokinetic Trial of Rebeccamycin Analog in Hepatobiliary Cancers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Liver Cancer
Keywords: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

  * 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

Primary outcomes:
measure: Determine the response rate in patients with advanced hepatobiliary carcinoma treated with rebeccamycin analogue.
timeFrame: Patients are followed every 3 months.
Secondary outcomes:
measure: Assess the toxicity associated with this drug in this patient population.
timeFrame: Patients are followed every 3 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
Study officials:
affiliation: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
name: Afshin Dowlati, MD
role: STUDY_CHAIR
References:
citation: 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):73-8. doi: 10.1007/s00280-009-1005-x. Epub 2009 Apr 28.
citation: 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.