An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Oxaliplatin and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Oxaliplatin and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of biweekly alvocidib when given in conjunction with oxaliplatin, 5-fluorouracil, and leucovorin calcium
Outcome Description:
Defined as the dose level immediately preceding the dose where 2 or more patients experienced dose-limiting toxicity.
Outcome Time Frame:
6 weeks
Safety Issue:
Yes
Principal Investigator
Gary Schwartz
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00055
NCT ID:
NCT00080990
Start Date:
February 2004
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan Kettering Cancer Center | New York, New York 10021 |
