A Phase I Clinical Trial of Sequential Pralatrexate Followed by a 48-hour Infusion of 5- Fluorouracil Given Every Other Week in Adult Patients With Solid Tumors
I. To determine the recommended dose of PDX (pralatrexate) given in combination with a fixed
dose of 5-FU (fluorouracil) administered as a 48-hour infusion given every other week.
I. To assess clinical response to therapy in subjects with measurable disease and time to
disease progression in all subjects.
II. To assess the toxicity profile of the combination of PDX and 5-FU. III. To determine the
pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity.
IV. To analyze polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase
(TS) and correlate with clinical toxicity.
OUTLINE: This is a dose-escalation study of pralatrexate.
Patients receive pralatrexate intravenously (IV) over 5 minutes on day 1 and fluorouracil IV
continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other week
Maximum tolerated dose will have been exceeded when 2 patients entered at a given dose level experience specified dose-limiting toxicities in the initial cycle.
During the initial course
University of Nebraska
United States: Institutional Review Board
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center||Omaha, Nebraska 68198-7680|