Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

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

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: 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

Relevance to patient case: not relevant