High-Dose Methotrexate in Treating Young Patients With Solid Tumors

NCT ID: NCT00513981

Last Updated: 2013-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2009-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Brain and Central Nervous System Tumors Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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leucovorin calcium

Intervention Type DRUG

methotrexate

Intervention Type DRUG

mass spectrometry

Intervention Type OTHER

pharmacological study

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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:


* 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


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

Exclusion Criteria

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

PRIOR CONCURRENT THERAPY:


* Received chemotherapy or biologic therapy within the past 4 weeks
* Received radiotherapy within the past 6 weeks
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Cancer and Leukaemia Group

OTHER

Sponsor Role lead

Principal Investigators

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Eddy J. Estlin

Role: PRINCIPAL_INVESTIGATOR

Royal Manchester Children's Hospital

Locations

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Our Lady's Hospital for Sick Children Crumlin

Dublin, , Ireland

Site Status

Birmingham Children's Hospital

Birmingham, England, United Kingdom

Site Status

Bristol Royal Hospital for Children

Bristol, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Site Status

University College Hospital

London, England, United Kingdom

Site Status

Great Ormond Street Hospital for Children

London, England, United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, England, United Kingdom

Site Status

Sir James Spence Institute of Child Health

Newcastle upon Tyne, England, United Kingdom

Site Status

Queen's Medical Centre

Nottingham, England, United Kingdom

Site Status

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Site Status

Children's Hospital - Sheffield

Sheffield, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Site Status

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Site Status

Royal Hospital for Sick Children

Edinburgh, Scotland, United Kingdom

Site Status

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Site Status

Childrens Hospital for Wales

Cardiff, Wales, United Kingdom

Site Status

Countries

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Ireland United Kingdom

Other Identifiers

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CDR0000560133

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU-20744

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2005-001757-13

Identifier Type: -

Identifier Source: secondary_id

CCLG-NAG-2005-13

Identifier Type: -

Identifier Source: org_study_id

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