Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

High-Dose Methotrexate in Treating Young Patients With Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Completed	21 and under	Other	CCLG-NAG-2005-13 NAG 2005 13, EU-20744, EUDRACT-2005-001757-13, NCT00513981

Objectives

1. 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.
2. To relate the methotrexate schedules investigated to the magnitude and duration of changes in plasma homocysteine and methionine.
3. 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.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

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

Patient Characteristics:

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

Expected Enrollment

Outcomes

Maximum tolerated infusion time for high-dose methotrexate

Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine

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.

Trial Contact Information

Trial Lead Organizations

Children's Cancer and Leukaemia Group

Eddy Estlin, Principal investigator		Ph: 44-161-922-2950

Related Information

PDQ® clinical trial CCLG-NAG-2005-09
PDQ® clinical trial CCLG-CNS-2001-4

Registry Information
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
Trial Start Date		2007-03-22
Trial Completion Date		2008-03-12
Registered in ClinicalTrials.gov		NCT00513981
Date Submitted to PDQ		2007-07-16
Information Last Verified		2009-06-14

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