Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors
Recruitment status was: Recruiting
RATIONALE: Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pralatrexate together with fluorouracil may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of pralatrexate when given together with fluorouracil in treating patients with recurrent solid tumors
Unspecified Adult Solid Tumor, Protocol Specific
Other: laboratory biomarker analysis
Genetic: DNA analysis
Other: high performance liquid chromatography
Genetic: polymerase chain reaction
Genetic: nucleic acid sequencing
Other: pharmacological study
Other: pharmacogenomic studies
Genetic: polymorphism analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other week [ Time Frame: During the initial course ] [ Designated as safety issue: Yes ]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.
- Clinical response to therapy in subjects with measurable disease and time to disease progression in all subjects [ Time Frame: After each two 4-week course ] [ Designated as safety issue: No ]
- Toxicity profile of the combination of PDX and 5-FU [ Time Frame: From the time the subject signs the consent form and ending 4 weeks following the final chemotherapy ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity [ Time Frame: Pre-treatment, end of infusion, at 15, 30, and 60 min, and then at 2, 4, 6, 8, 12, 22, 23, 24, 45, and 46 hours for PDX. At one-hour intervals times three prior to the end of the 48-hour infusion for 5-FU. ] [ Designated as safety issue: No ]
- Polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and correlate with clinical toxicity [ Time Frame: Prior to the first dose of protocol therapy ] [ Designated as safety issue: No ]
|Study Start Date:||September 2010|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate 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.
Other Names:Drug: fluorouracil
Other Names:Other: laboratory biomarker analysis
Correlative studiesGenetic: DNA analysis
Correlative studiesOther: high performance liquid chromatography
Other Name: HPLCGenetic: polymerase chain reaction
Other Name: PCRGenetic: nucleic acid sequencing
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: pharmacogenomic studies
Other Name: Pharmacogenomic StudyGenetic: polymorphism analysis
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01206465
|United States, Nebraska|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198-6805|
|Principal Investigator:||Jean Grem||University of Nebraska|