Phase I Study of Flavopiridol in Combination With 5-Fluorouracil, Leucovorin and Irinotecan in Patients With Advanced Malignancies
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I Study of Flavopiridol in Combination With 5-Fluorouracil, Leucovorin and Irinotecan in Patients With Advanced Malignancies
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Outcome Time Frame:
Up to 5 years
Safety Issue:
Yes
Principal Investigator
Keith Bible
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02389
NCT ID:
NCT00021073
Start Date:
May 2001
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
