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High-Dose Methotrexate in Treating Young Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00513981
Recruitment Status : Completed
First Posted : August 9, 2007
Last Update Posted : June 26, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as high-dose methotrexate work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as leucovorin calcium, may protect normal cells from the side effects of chemotherapy.

PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of high-dose methotrexate in treating patients with solid tumors.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific Drug: leucovorin calcium Drug: methotrexate Other: mass spectrometry Other: pharmacological study Phase 1

Detailed Description:


  • To determine the maximum tolerated time to exposure to high-dose methotrexate when administered as a continuous infusion at a dose of 6 g/m² per 24 hours.
  • To relate the methotrexate schedules investigated to the magnitude and duration of changes in plasma homocysteine and methionine.
  • To relate evidence of the systemic effect of methotrexate through changes in plasma homocysteine and methionine to any hepatic, neurological, or antiproliferative toxicity observed in the study group.

OUTLINE: Patients receive a continuous infusion of high-dose methotrexate IV over 24, 30, 36, or 42 hours depending on time of study entry. Beginning at hour 42 or 48, patients receive leucovorin calcium IV every 6 hours for 3 days or until plasma methotrexate concentration is < 0.2 µM. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study and analyzed for pharmacodynamic effects on plasma homocysteine and methionine by gas chromatography/mass spectrometry techniques.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study to Determine the Maximum Tolerated Time of Infusion for High-Dose Methotrexate, Administered as a Continuous Intravenous Infusion at a Dose of 6g/m² Per 24 Hours of Infusion Time
Study Start Date : March 2007
Actual Primary Completion Date : March 2008
Actual Study Completion Date : August 2009

Primary Outcome Measures :
  1. Maximum tolerated infusion time for high-dose methotrexate

Secondary Outcome Measures :
  1. Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven malignancy, including but not limited to, any of the following:

    • Patients with MRI findings in keeping with a diffuse intrinsic pontine glioma will be eligible without histological confirmation of tumor type

      • Patients with a diagnosis of diffuse intrinsic pontine glioma who are not eligible for the erlotinib hydrochloride phase I study (CCLG-NAG-2005-09)
    • Patients with relapsed ependymoma following the CCLG phase II study of intravenous etoposide (CCLG-CNS-2001-4) or prior to this are eligible at the discretion of the physician
    • Patients with relapsed osteogenic sarcoma, other soft tissue sarcomas, or other solid tumors may be suitable for this study at the discretion of the physician
  • Radiologically evaluable disease without bone marrow involvement


Inclusion criteria:

  • Lansky performance status (PS) 30-100% (for patients ≤ 12 years of age)
  • ECOG PS ≤ 2 (for patients ≥ 13 years of age)
  • Life expectancy ≥ 9 weeks
  • ANC > 1,000/mm³
  • Platelet count > 100,000/mm³
  • Hemoglobin > 9 g/dL
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN) for age
  • Serum total bilirubin normal
  • AST or ALT ≤ 2 times ULN
  • Glomerular filtration rate ≥ 60 mL/min
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion criteria:

  • Poor medical risk because of nonmalignant systemic disease or uncontrolled infection
  • Concurrent malignancies at other sites


Inclusion criteria:

  • Prophylactic trimethoprim-sulfamethoxazole must be stopped 1 week prior to methotrexate administration

Exclusion criteria:

  • Received chemotherapy or biologic therapy within the past 4 weeks
  • Received radiotherapy within the past 6 weeks

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00513981

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Our Lady's Hospital for Sick Children Crumlin
Dublin, Ireland, 12
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B4 6NH
Bristol Royal Hospital for Children
Bristol, England, United Kingdom, BS2 8BJ
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
University College Hospital
London, England, United Kingdom, NW1 2PCE
Great Ormond Street Hospital for Children
London, England, United Kingdom, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, England, United Kingdom, M27 4HA
Sir James Spence Institute of Child Health
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Queen's Medical Centre
Nottingham, England, United Kingdom, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ
Childrens Hospital for Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
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Principal Investigator: Eddy J. Estlin Royal Manchester Children's Hospital

Layout table for additonal information Identifier: NCT00513981     History of Changes
Other Study ID Numbers: CCLG-NAG-2005-13
CDR0000560133 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: August 9, 2007    Key Record Dates
Last Update Posted: June 26, 2013
Last Verified: June 2009
Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific
recurrent osteosarcoma
recurrent childhood soft tissue sarcoma
recurrent childhood ependymoma
untreated childhood brain stem glioma
recurrent childhood brain stem glioma
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms by Site
Nervous System Diseases
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors