High-Dose Methotrexate in Treating Young Patients With Solid Tumors
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Brain and Central Nervous System Tumors; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific
Intervention: leucovorin calcium (Drug); methotrexate (Drug); mass spectrometry (Procedure); pharmacological study (Procedure)
Phase: Phase 1
Status: Suspended
Sponsored by: Children's Cancer and Leukaemia Group Official(s) and/or principal investigator(s):
Eddy J. Estlin, Principal Investigator, Affiliation: Royal Manchester Children's Hospital
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.
Clinical Details
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 design: Treatment, Open Label
Primary outcome: Maximum tolerated infusion time for high-dose methotrexate
Secondary outcome: Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine
Detailed description:
OBJECTIVES:
- 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.
Eligibility
Minimum age: N/A.
Maximum age: 21 Years.
Gender(s): Both.
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
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
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
Locations and Contacts
Our Lady's Hospital for Sick Children Crumlin, Dublin 12, Ireland
Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom
Birmingham Children's Hospital, Birmingham, England B4 6NH, United Kingdom
Bristol Royal Hospital for Children, Bristol, England BS2 8BJ, United Kingdom
Children's Hospital - Sheffield, Sheffield, England S10 2TH, United Kingdom
Great Ormond Street Hospital for Children, London, England WC1N 3JH, United Kingdom
Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom
Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom
Oxford Radcliffe Hospital, Oxford, England 0X3 9DU, United Kingdom
Queen's Medical Centre, Nottingham, England NG7 2UH, United Kingdom
Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England L12 2AP, United Kingdom
Royal Manchester Children's Hospital, Manchester, England M27 4HA, United Kingdom
Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom
Sir James Spence Institute of Child Health, Newcastle-Upon-Tyne, England NE1 4LP, United Kingdom
Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom
University College Hospital, London, England NW1 2PCE, United Kingdom
Royal Belfast Hospital for Sick Children, Belfast, Northern Ireland BT12 6BE, United Kingdom
Royal Aberdeen Children's Hospital, Aberdeen, Scotland AB25 2ZG, United Kingdom
Royal Hospital for Sick Children, Glasgow, Scotland G3 8SJ, United Kingdom
Royal Hospital for Sick Children, Edinburgh, Scotland EH9 1LF, United Kingdom
Childrens Hospital for Wales, Cardiff, Wales CF14 4XW, United Kingdom
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: March 2007
Last updated: May 23, 2008
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