A Trial of Carboxypeptidase-G2 (CPDG2) and Thymidine for the Management of Patients With Methotrexate Toxicity and Renal Dysfunction

• Status: Completed
• Trial end date: 2001-01-01
• Target enrollment: 0
• Participant gender: All

Summary

High dose methotrexate with leucovorin rescue has demonstrated activity in numerous malignancies. Although high dose methotrexate is generally well tolerated, unpredictable life-threatening toxicity can occur. For patients who have markedly delayed clearance of methotrexate secondary to renal dysfunction, therapeutic options are few and are of limited efficacy. Carboxypeptidase-G2 inactivates methotrexate by hydrolyzing its C-terminal glutamate residue. Carboxypeptidase-G2 could be used to rescue patients with renal dysfunction and delayed methotrexate excretion, as it provides an alternative to renal clearance as a route of elimination.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Methotrexate

Criteria

Patients of any age at risk for life-threatening toxicity following MTX administration secondary to delayed drug excretion as defined by:

Plasma MTX concentration at least 10 micromoles/liter more than 42 hours after the start of the MTX infusion; OR

Creatinine at least 1.5 times the upper limit of normal or creatinine clearance less than 60 ml/sqm/min and delayed MTX excretion documented by plasma MTX concentration measurements (at least 2 standard deviations above the mean) at least 12 hours following MTX administration.