Phase I Study of High Dose Methotrexate With Simultaneous Trimetrexate and Leucovorin in Patients With Recurrent Osteosarcoma
- Determine the maximum tolerated dose of trimetrexate glucuronate when administered with
high-dose methotrexate and leucovorin calcium in patients with refractory or recurrent
- Determine the dose-limiting toxic effects of this regimen in these patients.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of trimetrexate glucuronate.
Patients receive high-dose methotrexate IV over 4 hours on days 1 and 8 and oral
trimetrexate glucuronate twice daily on days 2-6 and 9-13. Patients also receive leucovorin
calcium IV continuously over 24 hours or orally 2 or 4 times daily on days 9-14. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of trimetrexate glucuronate until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for this study within 2 years.
Primary Purpose: Treatment
Maximum tolerated dose (MTD) after 1 course of treatment
Paul A. Meyers, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|