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Combination Chemotherapy in Treating Patients Who Have Advanced Solid Tumors

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00020488
Collaborator
(none)
1
Location

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have advanced solid tumors.

Condition or Disease Intervention/Treatment Phase
  • Drug: FOLFIRI regimen
  • Drug: fluorouracil
  • Drug: irinotecan hydrochloride
  • Drug: leucovorin calcium
 Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Feb 1, 2001

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda Maryland United States 20892-1182

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Eva Szabo, MD, National Cancer Institute (NCI)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00020488
    Other Study ID Numbers:
    • CDR0000068548
    • NCI-01-C-0082
    • MB-NAVY-00-02
    • MB-NAVY-B00-038
    • NCT00021515
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Apr 30, 2015
    Last Verified:
    Sep 1, 2003
    Keywords provided by , ,
    unspecified adult solid tumor, protocol specific
    Additional relevant MeSH terms:
    Leucovorin
    Fluorouracil
    Irinotecan
    Calcium
    Levoleucovorin

    Study Results

    No Results Posted as of Apr 30, 2015