Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 29
Healthy volunteers: no

Brief summary:
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

Detailed description:
PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Arms:
arm 1: 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.

Interventions: intervention 1: pralatrexate intervention 2: fluorouracil intervention 3: laboratory biomarker analysis intervention 4: DNA analysis intervention 5: high performance liquid chromatography intervention 6: polymerase chain reaction intervention 7: nucleic acid sequencing intervention 8: pharmacological study intervention 9: pharmacogenomic studies intervention 10: polymorphism analysis
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Correlative studies intervention 4: Correlative studies intervention 5: Correlative studies intervention 6: Correlative studies intervention 7: Correlative studies intervention 8: Correlative studies intervention 9: Correlative studies intervention 10: Correlative studies

Protocol document: