Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors

NCT01206465 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 0238-10-FBNCI-14191
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Recommended Dose of PDX Given With a Fixed Dose of 5-FU

  Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other weekMaximum tolerated dose will have been exceeded when 2 patients entered at a given dose level experience specified dose-limiting toxicities in the initial cycle

  During the initial course (day 1 & 15 of a 4 week schedule)

Secondary Outcomes (6)

• Response to Therapy in Subjects With Measurable Disease

  restaging imaging done after each two 4-week course until time of progression (the maximum duration of PFS = 588 days)

• Number of Patients Experiencing Grade 3-4 Toxicity While Receiving the Combination of PDX and 5-FU

  ., "From the time the subject signs the consent form and ending 4 weeks following the final chemotherapy, an average of 3 years

• Pharmacokinetics of PDX- AUClast

  Pre-treatment, end of infusion, at 15, 30, and 60 min, and then at 2, 4, 6, 8, 12, 22, 23, 24, 45, and 46 hours for PDX.

• Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase

  Prior to the first dose of protocol therapy

• 5-FU Plasma Levels

  22, 23, 45 & 46 hours during the 48 hour infusion

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

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.

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

Interventions

pralatrexate DRUG

Given IV

Also known as: FOLOTYN, PDX

Treatment (enzyme inhibitor therapy)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (enzyme inhibitor therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy)

DNA analysis GENETIC

Correlative studies

Treatment (enzyme inhibitor therapy)

high performance liquid chromatography OTHER

Correlative studies

Also known as: HPLC

Treatment (enzyme inhibitor therapy)

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Treatment (enzyme inhibitor therapy)

nucleic acid sequencing GENETIC

Correlative studies

Also known as: Gene Sequencing, Molecular Biology, Nucleic Acid Sequencing

Treatment (enzyme inhibitor therapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzyme inhibitor therapy)

pharmacogenomic studies OTHER

Correlative studies

Also known as: Pharmacogenomic Study

Treatment (enzyme inhibitor therapy)

polymorphism analysis GENETIC

Correlative studies

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center, Eppley Cancer Center

Omaha, Nebraska, 68198-6805, United States

Location

Related Publications (1)

• 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 RESULT

MeSH Terms

Interventions

10-propargyl-10-deazaaminopterin; Fluorouracil; Chromatography, High Pressure Liquid; Polymerase Chain Reaction; Base Sequence; Pharmacogenomic Testing; Amplified Fragment Length Polymorphism Analysis

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chromatography, Liquid; Chromatography; Chemistry Techniques, Analytical; Investigative Techniques; Nucleic Acid Amplification Techniques; Genetic Techniques; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; DNA Fingerprinting

Results Point of Contact

• Title: Jean L Grem
• Organization: University of Nebraska Medical Center

jgrem@unmc.edu

402-559-5166

Study Officials

• Jean Grem

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2010
• First Posted: September 21, 2010
• Study Start: September 14, 2010
• Primary Completion: February 4, 2015
• Study Completion: June 1, 2017
• Last Updated: December 26, 2023
• Results First Posted: July 16, 2018

Record last verified: 2023-12

Locations

US (1)