Combination Chemotherapy in Treating Patients With Advanced Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00021073
First received: July 11, 2001
Last updated: December 10, 2013
Last verified: December 2013

July 11, 2001
December 10, 2013
May 2001
April 2006   (final data collection date for primary outcome measure)
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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00021073 on ClinicalTrials.gov Archive Site
Number of responses (complete response, partial response, stable disease, and progressive disease) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Summarized by simple descriptive summary statistics.
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy in Treating Patients With Advanced Cancer
Phase I Study of Flavopiridol in Combination With 5-Fluorouracil, Leucovorin and Irinotecan in Patients With Advanced Malignancies

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.

OBJECTIVES:

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

II. 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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • 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
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.

Interventions:
  • Drug: alvocidib
  • Drug: leucovorin calcium
  • Drug: fluorouracil
  • Drug: irinotecan hydrochloride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
90
Not Provided
April 2006   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00021073
NCI-2012-02389, NCI-2012-02389, CDR0000068745, MAYO-MC0014, NCI-2450, MC0014, 2450
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Keith Bible Mayo Clinic
National Cancer Institute (NCI)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP