High-Dose Methotrexate in Treating Young Patients With Solid Tumors

June 25, 2013 updated by: Children's Cancer and Leukaemia Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ireland
      • Dublin, Ireland, 12
        • Our Lady's Hospital for Sick Children Crumlin
  • United Kingdom
    • England
      • Birmingham, England, United Kingdom, B4 6NH
        • Birmingham Children's Hospital
      • Bristol, England, United Kingdom, BS2 8BJ
        • Bristol Royal Hospital for Children
      • Cambridge, England, United Kingdom, CB2 2QQ
        • Addenbrooke's Hospital
      • Leeds, England, United Kingdom, LS9 7TF
        • Leeds Cancer Centre at St. James's University Hospital
      • Leicester, England, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • Liverpool, England, United Kingdom, L12 2AP
        • Royal Liverpool Children's Hospital, Alder Hey
      • London, England, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital for Children
      • London, England, United Kingdom, NW1 2PCE
        • University College Hospital
      • Manchester, England, United Kingdom, M27 4HA
        • Royal Manchester Children's Hospital
      • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
        • Sir James Spence Institute of Child Health
      • Nottingham, England, United Kingdom, NG7 2UH
        • Queen's Medical Centre
      • Oxford, England, United Kingdom, 0X3 9DU
        • Oxford Radcliffe Hospital
      • Sheffield, England, United Kingdom, S10 2TH
        • Children's Hospital - Sheffield
      • Southampton, England, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Sutton, England, United Kingdom, SM2 5PT
        • Royal Marsden - Surrey
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, BT12 6BE
        • Royal Belfast Hospital for Sick Children
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB25 2ZG
        • Royal Aberdeen Children's Hospital
      • Edinburgh, Scotland, United Kingdom, EH9 1LF
        • Royal Hospital for Sick Children
      • Glasgow, Scotland, United Kingdom, G3 8SJ
        • Royal Hospital for Sick Children
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 4XW
        • Childrens Hospital for Wales

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated infusion time for high-dose methotrexate

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Cancer and Leukaemia Group

Investigators

  • Principal Investigator: Eddy J. Estlin, Royal Manchester Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

August 8, 2007

First Submitted That Met QC Criteria

August 8, 2007

First Posted (Estimate)

August 9, 2007

Study Record Updates

Last Update Posted (Estimate)

June 26, 2013

Last Update Submitted That Met QC Criteria

June 25, 2013

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCLG-NAG-2005-13
  • CDR0000560133 (Registry Identifier: PDQ (Physician Data Query))
  • EU-20744
  • EUDRACT-2005-001757-13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sarcoma

Clinical Trials on pharmacological study

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ghana

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe