Expired Study
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Omaha, Nebraska 68198


Purpose:

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


Study summary:

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.


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


Study is Available At:


Original ID:

238-10


NCT ID:

NCT01206465


Secondary ID:

NCI-2010-02014


Study Acronym:


Brief Title:

Pralatrexate and 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


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

19 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Nebraska


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

29


Enrollment Type:

Actual


Overall Contact Information

Official Name:Jean Grem
Principal Investigator
University of Nebraska

Study Dates

Start Date:September 2010
Completion Date:June 2017
Completion Type:Actual
Primary Completion Date:February 4, 2015
Primary Completion Type:Actual
Verification Date:July 2018
Last Changed Date:July 13, 2018
First Received Date:September 17, 2010
First Results Date:February 4, 2018

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Time to Disease Progression in All Participants
Time Frame:restaging imaging done after each two 4-week course until time of progression (longest time to progr
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Pharmacokinetics of 5-FU - Cmax Plasma Levels
Time Frame:22, 23, 45 & 46 hours during the 48 hour infusion
Safety Issues:False
Description:5-FU plasma levels
Outcome Type:Secondary Outcome
Measure:Number of Participants With Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase
Time Frame:Prior to the first dose of protocol therapy
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Pharmacokinetics of PDX- AUClast
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, a
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Number of Patients Experiencing Grade 3-4 Toxicity While Receiving 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 chemothe
Safety Issues:False
Description:patients remained on study as long as they did not progress, and wished to continue on study (no limit on number of cycles)
Outcome Type:Secondary Outcome
Measure:Number of Participants With Response to Therapy in Subjects With Measurable Disease
Time Frame:restaging imaging done after each two 4-week course until time of progression (the maximum duration
Safety Issues:False
Outcome Type:Primary Outcome
Measure: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 (day 1 & 15 of a 4 week schedule)
Safety Issues:False
Description: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

Study Interventions

Intervention Type:Genetic
Name:polymorphism analysis
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Intervention Type:Other
Name:pharmacogenomic studies
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Other Name:Pharmacogenomic Study
Intervention Type:Other
Name:pharmacological study
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Other Name:pharmacological studies
Intervention Type:Genetic
Name:nucleic acid sequencing
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Other Name:Gene Sequencing
Intervention Type:Genetic
Name:polymerase chain reaction
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Other Name:PCR
Intervention Type:Other
Name:high performance liquid chromatography
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Other Name:HPLC
Intervention Type:Genetic
Name:DNA analysis
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Treatment (enzyme inhibitor therapy)
Intervention Type:Drug
Name:fluorouracil
Description:Given IV
Arm Name:Treatment (enzyme inhibitor therapy)
Other Name:5-fluorouracil
Intervention Type:Drug
Name:pralatrexate
Description:Given IV
Arm Name:Treatment (enzyme inhibitor therapy)
Other Name:FOLOTYN

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (enzyme inhibitor therapy)
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.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Nebraska
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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.
PMID:26242208

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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