Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors

Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific

Intervention: pralatrexate (Drug); fluorouracil (Drug); laboratory biomarker analysis (Other); DNA analysis (Genetic); high performance liquid chromatography (Other); polymerase chain reaction (Genetic); nucleic acid sequencing (Genetic); pharmacological study (Other); pharmacogenomic studies (Other); polymorphism analysis (Genetic)

Phase: Phase 1

Status: Recruiting

Sponsored by: University of Nebraska

Official(s) and/or principal investigator(s):
Jean Grem, Principal Investigator, Affiliation: University of Nebraska

Overall contact:
Mary "Beth" Kos, RN BSN OCN, Phone: 402-559-4726, Email: mekos@unmc.edu

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

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

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other week

Secondary outcome:

Clinical response to therapy in subjects with measurable disease and time to disease progression in all subjects

Toxicity profile of the combination of PDX and 5-FU

Pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity

Polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and correlate with clinical toxicity

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.

Minimum age: 19 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Cancer patients who have failed standard therapy for their disease or for whom no

such therapy is available are eligible, for which 5-fluoropyrimdines, including 5-FU, or inhibitors of DHFR (dihydrofolate reductase), including pralatrexate, have the potential for therapeutic benefit

- Objectively measurable disease is preferred, but not required

- Performance status of 0-2 (Eastern Cooperative Oncology Group [ECOG])

- Prior treatment:

- The patient should have recovered from the toxicities associated with prior

chemotherapy (at least 3 weeks from prior therapy)

- At least two or more weeks should have elapsed since any radiotherapy, and the

patient should have recovered from the toxicity associated with such therapy

- If a recent surgical procedure has been performed, the patient should have recovered

from the surgery prior to entering this trial

- Absolute granulocyte count of 1500 per mcL or greater

- Platelet count of 100,000 per mcL or greater

- Serum bilirubin less than 1. 5 times the upper limits of the institutional normal

- Serum creatinine less than the upper limits of normal

- The patient must willingly give signed informed consent

Exclusion Criteria:

- Pregnant women and nursing mothers are ineligible; eligible patients of reproductive

potential should use adequate contraception if sexually active

- Serious concurrent medical illness which would jeopardize the ability of the patient

to receive the chemotherapy program outlined in this protocol with reasonable safety

- Patients with active infections requiring intravenous antibiotic therapy are not

eligible until the infection has resolved

- Patients who are human immunodeficiency virus (HIV) antibody positive and are

receiving highly active antiretroviral therapy (HAART) are ineligible

- Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and

trimethoprim/sulfamethoxazole will not be allowed

Mary "Beth" Kos, RN BSN OCN, Phone: 402-559-4726, Email: mekos@unmc.edu

UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, United States; Recruiting
Jean L. Grem, Phone: 402-559-3233, Email: jgrem@unmc.edu
Jean L. Grem, Principal Investigator

Starting date: September 2010
Last updated: August 15, 2011