Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors

University of Nebraska

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Other: laboratory biomarker analysis

Genetic: polymerase chain reaction

Drug: fluorouracil

Genetic: polymorphism analysis

Drug: pralatrexate

Other: pharmacogenomic studies

Genetic: DNA analysis

Other: pharmacological study

Other: high performance liquid chromatography

Genetic: nucleic acid sequencing

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01206465

NCI-14191 (Other Grant/Funding Number)

0238-10-FB

Details and patient eligibility

About

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

Full 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.

Enrollment

29 patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

29 participants in 1 patient group

Treatment (enzyme inhibitor therapy)

Experimental group

Description:

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.

Treatment: