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A Phase I & Pharmacologic Trial Of Sequential Irinotecan As A 24-Hour IV Infusion, Leucovorin, & Flurouracil As A 48-Hour IV Infusion In Adult Cancer Patients


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I & Pharmacologic Trial Of Sequential Irinotecan As A 24-Hour IV Infusion, Leucovorin, & Flurouracil As A 48-Hour IV Infusion In Adult Cancer Patients


OBJECTIVES:

- Determine the recommended phase II dose of irinotecan, leucovorin calcium, and
fluorouracil in patients with advanced solid tumors.

- Determine the toxic effects of this regimen in these patients.

- Determine the pharmacokinetic and pharmacodynamic profiles of irinotecan and
fluorouracil in patients treated with this regimen.

- Determine the correlation of polymorphisms in the promoter region of the thymidylate
synthase gene with clinical toxicity and response in patients treated with this
regimen.

- Determine the correlation of polymorphisms in the uridine diphosphate
glucuronosyltransferase 1A1 gene promoter with the extent of SN-38 glucuronidation and
severity of diarrhea in patients treated with this regimen.

- Assess any anti-tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of irinotecan and fluorouracil.

Patients receive irinotecan IV continuously over 24 hours on days 1 and 15 and leucovorin
calcium IV over 30 minutes followed by fluorouracil IV continuously over 48 hours on days 2
and 16. Treatment repeats every 28 days for at least 2 courses in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated
dose (MTD) is determined. Once the MTD of irinotecan has been determined, additional cohorts
receive escalating doses of fluorouracil until the MTD is determined. The MTD is defined as
the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting
toxicity.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study within 20
months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed advanced solid tumor that has failed standard therapy or for
which no standard therapy exists

- Locally advanced, unresectable, primary or recurrent disease OR

- Metastatic disease

- Previously untreated disease allowed provided this regimen represents reasonable
first-line therapy

- No leukemia or lymphoma

- No primary CNS malignancy or CNS metastases

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Absolute granulocyte count at least 2,000/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 1.6 mg/dL

- AST/ALT no greater than 4 times upper limit of normal

Renal:

- Creatinine no greater than 1.6 mg/dL

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No other serious concurrent illness that would preclude study

- No active infection requiring IV antibiotics

- No known hypersensitivity to irinotecan

- No marked intolerance to fluorouracil

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- More than 4 weeks since prior immunotherapy and recovered

Chemotherapy:

- More than 4 weeks since prior chemotherapy (at least 6 weeks for nitrosoureas or
mitomycin) and recovered

- Prior short-infusion irinotecan allowed

- Prior fluorouracil allowed

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 2 weeks since prior radiotherapy and recovered

- At least 8 weeks since prior strontium chloride Sr 89

Surgery:

- Recovered from prior surgery

Other:

- No concurrent cimetidine

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Eva Szabo, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

CDR0000068548

NCT ID:

NCT00020488

Start Date:

February 2001

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182