Flavopiridol, Oxaliplatin, Fluorouracil, and Leucovorin in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00080990

Purpose

RATIONALE: Drugs used in chemotherapy, such as flavopiridol, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop tumor cells from dividing so they stop growing or die. Flavopiridol may also make tumor cells more sensitive to chemotherapy. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of flavopiridol when given together with oxaliplatin, fluorouracil, and leucovorin in treating patients with advanced solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: alvocidib Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Alvocidib Flavopiridol Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

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

Primary Outcome Measures:

Recommended phase II dose as assessed by NCI toxicity scale during 4-6 weeks of treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response as assessed by RECIST criteria every 8 weeks [ Designated as safety issue: No ]

Estimated Enrollment:	46
Study Start Date:	February 2004
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of flavopiridol when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.
Determine the pharmacokinetics of this regimen in these patients.
Determine, preliminarily, the therapeutic activity of this regimen in these patients.

Secondary

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

PROJECTED ACCRUAL: A total of 3-46 patients will be accrued for this study within approximately 2 years.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

WBC ≥ 3,500/mm^3
Neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 1.5 mg/dL
AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for liver metastases)

Renal

Creatinine ≤ 1.5 mg/dL

Cardiovascular

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

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 2 weeks since prior immunotherapy

Chemotherapy

At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
No prior flavopiridol

Endocrine therapy

Not specified

Radiotherapy

At least 2 weeks since prior radiotherapy

Surgery

Not specified

Other

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00080990

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Gary K. Schwartz, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000357606, MSKCC-03146, NCI-6365
Study First Received:	April 7, 2004
Last Updated:	May 2, 2009
ClinicalTrials.gov Identifier:	NCT00080990 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Antimetabolites
Vitamin B Complex
Immunologic Factors
Leucovorin
Trace Elements
Folinic Acid
Immunosuppressive Agents

Protein Kinase Inhibitors
Flavopiridol
Calcium, Dietary
Oxaliplatin
Fluorouracil
Vitamins
Micronutrients

Additional relevant MeSH terms:

Antimetabolites
Vitamin B Complex
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Leucovorin
Enzyme Inhibitors

Protein Kinase Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Flavopiridol
Oxaliplatin
Vitamins
Fluorouracil
Therapeutic Uses
Growth Inhibitors
Micronutrients

ClinicalTrials.gov processed this record on September 10, 2009