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

NCT00001298 | Completed Phase 1

• 2 other identifiers: 92013492-C-0134
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Diseases

Keywords

Antibody; DAMPA; Enzyme; Kidney; Pharmacokinetics; Thymidine; Toxicity

Interventions

carboxypeptidase-G2 DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Adamson PC, Balis FM, McCully CL, Godwin KS, Poplack DG. Methotrexate pharmacokinetics following administration of recombinant carboxypeptidase-G2 in rhesus monkeys. J Clin Oncol. 1992 Aug;10(8):1359-64. doi: 10.1200/JCO.1992.10.8.1359.

  PMID: 1634927 BACKGROUND

• Widemann BC, Hetherington ML, Murphy RF, Balis FM, Adamson PC. Carboxypeptidase-G2 rescue in a patient with high dose methotrexate-induced nephrotoxicity. Cancer. 1995 Aug 1;76(3):521-6. doi: 10.1002/1097-0142(19950801)76:33.0.co;2-m.

  PMID: 8625136 BACKGROUND

• Widemann BC, Balis FM, Murphy RF, Sorensen JM, Montello MJ, O'Brien M, Adamson PC. Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction. J Clin Oncol. 1997 May;15(5):2125-34. doi: 10.1200/JCO.1997.15.5.2125.

  PMID: 9164227 BACKGROUND

MeSH Terms

Conditions

Kidney Diseases

Interventions

gamma-Glutamyl Hydrolase

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Carboxypeptidases; Exopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: March 1, 1992
• Study Completion: January 1, 2001
• Last Updated: March 4, 2008

Record last verified: 2000-02

Locations

US (1)