Back to resultsHigh-Dose Methotrexate in Treating Young Patients With Solid Tumors
Primary Purpose
Brain and Central Nervous System Tumors, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
leucovorin calcium
methotrexate
mass spectrometry
pharmacological study
Sponsored by
About this trial
This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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
Eligibility 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
Sites / Locations
- Our Lady's Hospital for Sick Children Crumlin
- Birmingham Children's Hospital
- Bristol Royal Hospital for Children
- Addenbrooke's Hospital
- Leeds Cancer Centre at St. James's University Hospital
- Leicester Royal Infirmary
- Royal Liverpool Children's Hospital, Alder Hey
- University College Hospital
- Great Ormond Street Hospital for Children
- Royal Manchester Children's Hospital
- Sir James Spence Institute of Child Health
- Queen's Medical Centre
- Oxford Radcliffe Hospital
- Children's Hospital - Sheffield
- Southampton General Hospital
- Royal Marsden - Surrey
- Royal Belfast Hospital for Sick Children
- Royal Aberdeen Children's Hospital
- Royal Hospital for Sick Children
- Royal Hospital for Sick Children
- Childrens Hospital for Wales
Outcomes
Primary Outcome Measures
Maximum tolerated infusion time for high-dose methotrexate
Secondary Outcome Measures
Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine
Full Information
NCT ID
NCT00513981
First Posted
August 8, 2007
Last Updated
June 25, 2013
Sponsor
Children's Cancer and Leukaemia Group
1. Study Identification
Unique Protocol Identification Number
NCT00513981
Brief Title
High-Dose Methotrexate in Treating Young Patients With Solid Tumors
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 Type
Interventional
2. Study Status
Record Verification Date
June 2009
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
August 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Children's Cancer and Leukaemia Group
4. Oversight
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Other
Intervention Name(s)
mass spectrometry
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Maximum tolerated infusion time for high-dose methotrexate
Secondary Outcome Measure Information:
Title
Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine
10. Eligibility
Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eddy J. Estlin
Organizational Affiliation
Royal Manchester Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Our Lady's Hospital for Sick Children Crumlin
City
Dublin
ZIP/Postal Code
12
Country
Ireland
Facility Name
Birmingham Children's Hospital
City
Birmingham
State/Province
England
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Bristol Royal Hospital for Children
City
Bristol
State/Province
England
ZIP/Postal Code
BS2 8BJ
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Leeds Cancer Centre at St. James's University Hospital
City
Leeds
State/Province
England
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
State/Province
England
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Royal Liverpool Children's Hospital, Alder Hey
City
Liverpool
State/Province
England
ZIP/Postal Code
L12 2AP
Country
United Kingdom
Facility Name
University College Hospital
City
London
State/Province
England
ZIP/Postal Code
NW1 2PCE
Country
United Kingdom
Facility Name
Great Ormond Street Hospital for Children
City
London
State/Province
England
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
State/Province
England
ZIP/Postal Code
M27 4HA
Country
United Kingdom
Facility Name
Sir James Spence Institute of Child Health
City
Newcastle-Upon-Tyne
State/Province
England
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Queen's Medical Centre
City
Nottingham
State/Province
England
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Facility Name
Oxford Radcliffe Hospital
City
Oxford
State/Province
England
ZIP/Postal Code
0X3 9DU
Country
United Kingdom
Facility Name
Children's Hospital - Sheffield
City
Sheffield
State/Province
England
ZIP/Postal Code
S10 2TH
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Royal Marsden - Surrey
City
Sutton
State/Province
England
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Royal Belfast Hospital for Sick Children
City
Belfast
State/Province
Northern Ireland
ZIP/Postal Code
BT12 6BE
Country
United Kingdom
Facility Name
Royal Aberdeen Children's Hospital
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB25 2ZG
Country
United Kingdom
Facility Name
Royal Hospital for Sick Children
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH9 1LF
Country
United Kingdom
Facility Name
Royal Hospital for Sick Children
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G3 8SJ
Country
United Kingdom
Facility Name
Childrens Hospital for Wales
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
12. IPD Sharing Statement
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High-Dose Methotrexate in Treating Young Patients With Solid Tumors
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