Combination Chemotherapy in Treating Patients With Advanced Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00021073
Collaborator
(none)
90
1
1

Study Details

Study Description

Brief Summary

Phase I trial to study the effectiveness of combining flavopiridol, fluorouracil, and leucovorin with or without irinotecan in treating patients who have advanced cancer. 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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

OBJECTIVES:
  1. Determine the maximum tolerated dose of flavopiridol, fluorouracil, and leucovorin calcium with or without irinotecan in patients with advanced malignancy.

  2. Assess the toxic effects of these regimens in these patients. III. Determine the clinical response in patients treated with these regimens.

OUTLINE: This a dose-escalation study of flavopiridol (FLAVO), fluorouracil (5-FU), and irinotecan. Patients are assigned to 1 of 2 groups. Groups I and II are conducted sequentially.

Group I: Patients receive FLAVO IV over 24 hours on day 1 and leucovorin calcium (CF) IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the maximum tolerated doses (MTD) are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Group II: Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and 5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined. The MTD is defined as in group I.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A maximum of 57-90 patients will be accrued for this study within 18 months.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Study of Flavopiridol in Combination With 5-Fluorouracil, Leucovorin and Irinotecan in Patients With Advanced Malignancies
Study Start Date :
May 1, 2001
Actual Primary Completion Date :
Apr 1, 2006

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (alvocidib, combination chemotherapy)

Group I: Patients receive FLAVO IV over 24 hours on day 1 and CF IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the MTD are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and 5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined. The MTD is defined as in group I.

Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
  • Drug: leucovorin calcium
    Given IV
    Other Names:
  • CF
  • CFR
  • LV
  • Drug: fluorouracil
    Given IV
    Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
  • Drug: irinotecan hydrochloride
    Given IV
    Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
  • Outcome Measures

    Primary Outcome Measures

    1. Number and severity of toxicity incidents of alvocidib, 5-fluorouracil, leucovorin calcium with and without irinotecan hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [Up to 5 years]

    Secondary Outcome Measures

    1. Number of responses (complete response, partial response, stable disease, and progressive disease) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) [Up to 5 years]

      Summarized by simple descriptive summary statistics.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically confirmed malignancy

    • Unresectable tumor

    • No known standard therapy with curative potential or capability of extending life expectancy

    • No untreated CNS metastases

    • Performance status - ECOG 0-2

    • At least 12 weeks

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

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

    • Hemoglobin at least 8 g/dL

    • Direct bilirubin no greater than upper limit of normal (ULN)

    • AST no greater than 3 times ULN (5 times ULN if liver metastases present)

    • Creatinine no greater than 1.5 times ULN

    • No New York Heart Association class III or IV heart disease

    • No seizure disorder

    • No uncontrolled infection

    • No baseline diarrhea, defined as at least 4 loose or liquid stools/day

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective contraception

    • More than 4 weeks since prior biologic therapy

    • More than 4 weeks since prior immunotherapy

    • No concurrent immunotherapy

    • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and fully recovered from acute reversible effects

    • No other concurrent chemotherapy

    • More than 4 weeks since prior radiotherapy

    • No prior radiotherapy to more than 25% of bone marrow

    • No concurrent radiotherapy

    • No other concurrent ancillary investigational therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Keith Bible, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00021073
    Other Study ID Numbers:
    • NCI-2012-02389
    • NCI-2012-02389
    • CDR0000068745
    • MAYO-MC0014
    • NCI-2450
    • MC0014
    • 2450
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Dec 11, 2013
    Last Verified:
    Dec 1, 2013

    Study Results

    No Results Posted as of Dec 11, 2013