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Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors

This study is currently recruiting participants.
Verified August 2011 by University of Nebraska
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT01206465
First received: September 17, 2010
Last updated: August 15, 2011
Last verified: August 2011
History of Changes
  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


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
 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
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Clinical response to therapy in subjects with measurable disease and time to disease progression in all subjects [ Time Frame: After each two 4-week course ] [ Designated as safety issue: No ]
  • Toxicity profile of 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 chemotherapy ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity [ 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, and 46 hours for PDX. At one-hour intervals times three prior to the end of the 48-hour infusion for 5-FU. ] [ Designated as safety issue: No ]
  • Polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and correlate with clinical toxicity [ Time Frame: Prior to the first dose of protocol therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: September 2010
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Drug: pralatrexate
Given IV
Other Names:
  • FOLOTYN
  • PDX
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: laboratory biomarker analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Other: high performance liquid chromatography
Correlative studies
Other Name: HPLC
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Genetic: nucleic acid sequencing
Correlative studies
Other Names:
  • Gene Sequencing
  • Molecular Biology, Nucleic Acid Sequencing
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Genetic: polymorphism analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01206465

Contacts
Contact: Mary "Beth" Kos, RN BSN OCN 402-559-4726 mekos@unmc.edu
Contact: Marsha Ketcham, RN OCN 402-559-5286 mketcham@unmc.edu

Locations
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Jean L. Grem     402-559-3233     jgrem@unmc.edu    
Principal Investigator: Jean L. Grem            
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jean Grem University of Nebraska
  More Information

No publications provided

Responsible Party: Grem, Jean, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT01206465     History of Changes
Other Study ID Numbers: 238-10, NCI-2010-02014
Study First Received: September 17, 2010
Last Updated: August 15, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Fluorouracil
Aminopterin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
 Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Folic Acid Antagonists
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013