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
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: alvocidib
Drug: leucovorin calcium
Drug: fluorouracil
Drug: irinotecan hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 90
Study Start Date: May 2001
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00021073

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Keith Bible Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00021073     History of Changes
Other Study ID Numbers: NCI-2012-02389, NCI-2012-02389, CDR0000068745, MAYO-MC0014, NCI-2450, MC0014, 2450
Study First Received: July 11, 2001
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fluorouracil
Irinotecan
Alvocidib
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Growth Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014