Brain and Central Nervous System TumorsPhase 1NCT00513981
High-Dose Methotrexate in Treating Young Patients With Solid Tumors
A Phase 1 study testing leucovorin calcium, methotrexate and mass spectrometry in people with Brain and Central Nervous System Tumors and Sarcoma, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific
- What is being tested?
- leucovorin calcium, methotrexate and mass spectrometry
- How many people
- 36 participants
- Where
- 21 sitesin 2 countries
- Study dates
- Mar 2007to Aug 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United Kingdom20 sites
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, AB25 2ZG
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, BT12 6BE
Birmingham Children's Hospital
Birmingham, England, B4 6NH
Bristol Royal Hospital for Children
Bristol, England, BS2 8BJ
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Childrens Hospital for Wales
Cardiff, Wales, CF14 4XW
Royal Hospital for Sick Children
Edinburgh, Scotland, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, G3 8SJ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Leicester Royal Infirmary
Leicester, England, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, L12 2AP
University College Hospital
London, England, NW1 2PCE
Great Ormond Street Hospital for Children
London, England, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, England, M27 4HA
Sir James Spence Institute of Child Health
Newcastle upon Tyne, England, NE1 4LP
Queen's Medical Centre
Nottingham, England, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, S10 2TH
Southampton General Hospital
Southampton, England, SO16 6YD
Royal Marsden - Surrey
Sutton, England, SM2 5PT
About this study
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
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.
Read the 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.
- Conditions
- Brain and Central Nervous System Tumors, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific
- Being tested
- leucovorin calcium, methotrexate, mass spectrometry, pharmacological study
- 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
- Medical subject headings
- Central Nervous System Neoplasms, Sarcoma, Osteosarcoma, Familial ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methotrexateDrug
mass spectrometryOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated infusion time for high-dose methotrexate
Secondary outcomes (1)
Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2007 (estimated)
- Study startMar 2007
- Primary completionMar 2008
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Cancer and Leukaemia Group
- Sponsor type
- University, hospital or other
- Investigators
- Eddy J. Estlin, Principal investigator, Royal Manchester Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00513981
- Sponsor's protocol ID
- CCLG-NAG-2005-13
- Other IDs
- CDR0000560133, EU-20744, EUDRACT-2005-001757-13
- Status last verified
- Jun 2009
- First submitted
- 8 Aug 2007
- Last updated
- 26 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00513981
- Acronym / sponsor ID
- CCLG-NAG-2005-13
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Children's Cancer and Leukaemia GroupUniversity, hospital or other
- Study start
- Mar 2007
- Primary completion
- Mar 2008 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 9 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (5 listed)
- Poor medical risk because of nonmalignant systemic disease or uncontrolled infection
- Concurrent malignancies at other sites
- Received chemotherapy or biologic therapy within the past 4 weeks
- Received radiotherapy within the past 6 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| leucovorin calcium | Drug | – |
| methotrexate | Drug | – |
| mass spectrometry | Other | – |
| pharmacological study | Other | – |
Primary outcome
Maximum tolerated infusion time for high-dose methotrexate
1 secondary outcome
Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eddy J. Estlin principal investigator
Royal Manchester Children's Hospital
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing leucovorin calcium, methotrexate and mass spectrometry in people with Brain and Central Nervous System Tumors and Sarcoma, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated infusion time for high-dose methotrexate. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2013.