Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors

NCT ID: NCT01206465

Last Updated: 2023-12-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-14

Study Completion Date

2017-06-01

Brief Summary

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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

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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.

Conditions

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Unspecified Adult Solid Tumor, Protocol Specific

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

pralatrexate

Intervention Type DRUG

Given IV

fluorouracil

Intervention Type DRUG

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

DNA analysis

Intervention Type GENETIC

Correlative studies

high performance liquid chromatography

Intervention Type OTHER

Correlative studies

polymerase chain reaction

Intervention Type GENETIC

Correlative studies

nucleic acid sequencing

Intervention Type GENETIC

Correlative studies

pharmacological study

Intervention Type OTHER

Correlative studies

pharmacogenomic studies

Intervention Type OTHER

Correlative studies

polymorphism analysis

Intervention Type GENETIC

Correlative studies

Interventions

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pralatrexate

Given IV

Intervention Type DRUG

fluorouracil

Given IV

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

DNA analysis

Correlative studies

Intervention Type GENETIC

high performance liquid chromatography

Correlative studies

Intervention Type OTHER

polymerase chain reaction

Correlative studies

Intervention Type GENETIC

nucleic acid sequencing

Correlative studies

Intervention Type GENETIC

pharmacological study

Correlative studies

Intervention Type OTHER

pharmacogenomic studies

Correlative studies

Intervention Type OTHER

polymorphism analysis

Correlative studies

Intervention Type GENETIC

Other Intervention Names

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FOLOTYN PDX 5-fluorouracil 5-Fluracil 5-FU HPLC PCR Gene Sequencing Molecular Biology, Nucleic Acid Sequencing pharmacological studies Pharmacogenomic Study

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Nebraska

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean Grem

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

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University of Nebraska Medical Center, Eppley Cancer Center

Omaha, Nebraska, United States

Site Status

Countries

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United States

References

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Grem JL, Kos ME, Evande RE, Meza JL, Schwarz JK. A phase 1 clinical trial of sequential pralatrexate followed by a 48-hour infusion of 5-fluorouracil given every other week in adult patients with solid tumors. Cancer. 2015 Nov 1;121(21):3862-8. doi: 10.1002/cncr.29504. Epub 2015 Aug 4.

Reference Type RESULT
PMID: 26242208 (View on PubMed)

Other Identifiers

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NCI-14191

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

0238-10-FB

Identifier Type: -

Identifier Source: org_study_id