Alvocidib, Oxaliplatin, Fluorouracil, and Leucovorin Calcium in Treating Patients With Advanced Solid Tumors

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00080990
Collaborator
(none)
46
1
1

Study Details

Study Description

Brief Summary

This phase I trial is studying the side effects and best dose of alvocidib when given together with oxaliplatin, fluorouracil, and leucovorin calcium in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as alvocidib, oxaliplatin, fluorouracil, and leucovorin calcium, work in different ways to stop tumor cells from dividing so they stop growing or die. Alvocidib may also make tumor cells more sensitive to chemotherapy. Combining more than one chemotherapy 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 when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.

  2. Determine the pharmacokinetics of this regimen in these patients. III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.

  3. Determine the dose-limiting toxicity and the recommended phase II dose of flavopiridol when administered with this regimen in these patients.

  4. Determine the safety and tolerability of this regimen in these patients. VI. Correlate p21, p53, and apoptotic markers with response in patients treated with this regimen.

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

Patients receive alvocidib intravenously (IV) over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of alvocidib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose.

Study Design

Study Type:
Interventional
Actual Enrollment :
46 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Oxaliplatin and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
Study Start Date :
Feb 1, 2004
Actual Primary Completion Date :
Apr 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (alvocidib with oxaliplatin, 5-FU, leucovorin)

Patients receive alvocidib IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. 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 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose.

Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
  • Drug: fluorouracil
    Given IV
    Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
  • Drug: oxaliplatin
    Given IV
    Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
  • Drug: leucovorin calcium
    Given IV
    Other Names:
  • CF
  • CFR
  • LV
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum tolerated dose of biweekly alvocidib when given in conjunction with oxaliplatin, 5-fluorouracil, and leucovorin calcium [6 weeks]

      Defined as the dose level immediately preceding the dose where 2 or more patients experienced dose-limiting toxicity.

    Secondary Outcome Measures

    1. Dose-limiting toxicity as defined by the occurrence of Grade 4 hematologic toxicity, Grade 3 or 4 non-hematologic toxicity including diarrhea despite antidiarrheal prophylaxis, or any delay in treatment resulting in less than 3 treatments in 6 weeks [6 weeks]

    2. Recommended phase II dose of alvocidib [6 weeks]

    Eligibility Criteria

    Criteria

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

    • Refractory to standard therapy or no standard therapy exists

    • Evaluable disease

    • No known untreated CNS metastases

    • Patients who have undergone local treatment for brain metastases and whose brain metastases are stable by repeat imaging study performed ≤ 4 weeks after treatment are allowed

    • No primary CNS tumors

    • Performance status - Karnofsky 60-100%

    • WBC ≥ 3,500/mm^3

    • Neutrophil count ≥ 1,500/mm^3

    • Platelet count ≥ 100,000/mm^3

    • Bilirubin ≤ 1.5 mg/dL

    • AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for liver metastases)

    • Creatinine ≤ 1.5 mg/dL

    • No cardiac arrhythmias within the past 6 months

    • No congestive heart failure within the past 6 months

    • No myocardial infarction within the past 6 months

    • No arterial or venous thrombosis within the past year

    • No peripheral neuropathy > grade 1

    • No other medical condition that would preclude study participation

    • No serious or uncontrolled infection

    • HIV negative

    • Not pregnant or nursing

    • No nursing during and for 2 months after study participation

    • Negative pregnancy test

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

    • At least 2 weeks since prior immunotherapy

    • At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)

    • No prior flavopiridol

    • At least 2 weeks since prior radiotherapy

    • Recovered from all prior therapy

    • No concurrent therapy for thrombosis

    • Prophylaxis for central lines or deep vein thrombosis allowed

    • No other concurrent investigational medications

    • No concurrent vitamins, antioxidants, or herbal preparations and supplements

    • Concurrent single-tablet multivitamin allowed

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Memorial Sloan-Kettering Cancer Center New York New York United States 10065

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Gary Schwartz, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00080990
    Other Study ID Numbers:
    • NCI-2009-00055
    • NCI-2009-00055
    • MSKCC-03146
    • CDR0000357606
    • NCI-6365
    • 03-146A
    • 6365
    • U01CA069856
    • NCT01645501
    • NCT01664299
    First Posted:
    Apr 8, 2004
    Last Update Posted:
    Dec 16, 2013
    Last Verified:
    Dec 1, 2013

    Study Results

    No Results Posted as of Dec 16, 2013