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

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ClinicalTrials.gov Identifier: NCT00080990
Recruitment Status : Completed
First Posted : April 8, 2004
Last Update Posted : December 16, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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
Unspecified Adult Solid Tumor, Protocol Specific Drug: alvocidib Drug: fluorouracil Drug: oxaliplatin Drug: leucovorin calcium Phase 1

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of flavopiridol when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.

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

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

V. 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.

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Study Type : Interventional  (Clinical Trial)
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 : February 2004
Actual Primary Completion Date : April 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Calcium

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




Primary Outcome Measures :
  1. Maximum tolerated dose of biweekly alvocidib when given in conjunction with oxaliplatin, 5-fluorouracil, and leucovorin calcium [ Time Frame: 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 [ Time Frame: 6 weeks ]
  2. Recommended phase II dose of alvocidib [ Time Frame: 6 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00080990


Locations
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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Gary Schwartz Memorial Sloan Kettering Cancer Center
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00080990    
Obsolete Identifiers: NCT01645501, NCT01664299
Other Study ID Numbers: NCI-2009-00055
NCI-2009-00055 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MSKCC-03146
CDR0000357606
NCI-6365
03-146A ( Other Identifier: Memorial Sloan-Kettering Cancer Center )
6365 ( Other Identifier: CTEP )
U01CA069856 ( U.S. NIH Grant/Contract )
First Posted: April 8, 2004    Key Record Dates
Last Update Posted: December 16, 2013
Last Verified: December 2013
Additional relevant MeSH terms:
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Neoplasms
Leucovorin
Fluorouracil
Oxaliplatin
Alvocidib
Calcium
Levoleucovorin
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors