High-Dose Methotrexate in Treating Young Patients With Solid Tumors

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00513981
• Other study ID #: CCLG-NAG-2005-13
• Secondary ID: CDR0000560133EU-
• Status: Completed
• Phase: Phase 1
• First received: August 8, 2007
• Last updated: June 25, 2013
• Start date: March 2007
• Est. completion date: August 2009

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2009
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• leucovorin calcium

• methotrexate

Other:
• mass spectrometry

• pharmacological study

Locations

Country	Name	City	State
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Bristol Royal Hospital for Children	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	University College Hospital	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated infusion time for high-dose methotrexate			No
Secondary	Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine			No