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Flavopiridol and Irinotecan in Treating Patients With Advanced Solid Tumors

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00006485
Collaborator
National Cancer Institute (NCI) (NIH)
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 combining flavopiridol with irinotecan in treating patients who have locally advanced or metastatic solid tumors.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of flavopiridol when combined with irinotecan in patients with advanced solid tumors.

  • Determine the clinical pharmacokinetics of this regimen, as well as the plasma levels of the active metabolite SN-38 and metabolic product SN-38 glucuronide in these patients.

  • Determine, in a preliminary manner, the therapeutic activity of this regimen in these patients.

  • Determine the role of p21 relative to treatment response and apoptosis in these patients treated with this regimen.

OUTLINE: This is a dose-escalation, open-label, non-randomized study of flavopiridol.

Patients receive irinotecan IV over 30 minutes followed 7 hours later by flavopiridol IV over 1 hour on days 1, 8, 15, and 22. Treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. During the first week of the second course, patients receive flavopiridol alone on day 1 and irinotecan alone on day 2.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients in the initial cohort experience dose limiting toxicity during the first course of treatment. An additional 10 patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 44-50 patients will be accrued for this study within 1 year.

Study Design

Study Type:
Interventional
Allocation:
Non-Randomized
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Labeled, Non-Randomized Phase I Study Of Flavopiridol Administered With Irinotecan (CPT-11) In Patients With Advanced Solid Tumors
Study Start Date :
Sep 1, 2000
Actual Primary Completion Date :
Dec 1, 2003

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 proven locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists

    • Eligible for treatment at the maximum tolerated dose only if disease accessible for tissue biopsy by Tru-Cut, CT guidance, or endoscopy

    • Pleural effusions or abdominal ascites do not constitute adequate tissue for biopsy

    • No known CNS metastasis or primary CNS tumor

    PATIENT CHARACTERISTICS:
    Age:
    • 18 and over
    Performance status:
    • Karnofsky 60-100%
    Life expectancy:
    • Not specified
    Hematopoietic:

    • WBC at least 3,500/mm^3

    • Total neutrophil count at least 1,500/mm^3

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

    Hepatic:

    • Bilirubin no greater than 1.5 mg/dL

    • SGOT and SGPT no greater than 2.5 times upper limit of normal

    Renal:
    • Creatinine no greater than 1.5 mg/dL
    Cardiovascular:
    • No cardiac arrhythmias, congestive heart failure, or myocardial infarction within the past 6 months
    Other:

    • Not pregnant or nursing (during and for at least 2 months after study)

    • Negative pregnancy test

    • Fertile patients must use effective contraception during and for at least 2 months after study

    • No concurrent serious or uncontrolled infection

    • HIV negative

    • No other medical condition that would preclude study participation

    PRIOR CONCURRENT THERAPY:
    Biologic therapy:
    • At least 4 weeks since prior immunotherapy and recovered
    Chemotherapy:

    • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

    • Prior irinotecan allowed

    Endocrine therapy:
    • Not specified
    Radiotherapy:
    • At least 4 weeks since prior radiotherapy and recovered
    Surgery:
    • See Disease Characteristics
    Other:

    • Recovered from prior therapy

    • No other concurrent investigational medication

    • No concurrent vitamins (except a single multivitamin tablet), antioxidants, or herbal preparations or supplements

    • No concurrent subcutaneous heparin or heparinoids

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Memorial Sloan-Kettering Cancer Center New York New York United States 10021

    Sponsors and Collaborators

    • Memorial Sloan Kettering Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Gary K. Schwartz, MD, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00006485
    Other Study ID Numbers:
    • CDR0000068316
    • MSKCC-00091
    • NCI-2272
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Dec 15, 2009
    Last Verified:
    Jun 1, 2003
    Keywords provided by , ,
    unspecified adult solid tumor, protocol specific
    Additional relevant MeSH terms:
    Neoplasms
    Irinotecan
    Alvocidib

    Study Results

    No Results Posted as of Dec 15, 2009