Back to resultsA Trial of Carboxypeptidase-G2 (CPDG2) and Thymidine for the Management of Patients With Methotrexate Toxicity and Renal Dysfunction
Primary Purpose
Kidney Diseases
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
carboxypeptidase-G2
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Diseases focused on measuring Antibody, DAMPA, Enzyme, Kidney, Pharmacokinetics, Thymidine, Toxicity
Eligibility 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.
Sites / Locations
- National Cancer Institute (NCI)
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00001298
First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00001298
Brief Title
A Trial of Carboxypeptidase-G2 (CPDG2) and Thymidine for the Management of Patients With Methotrexate Toxicity and Renal Dysfunction
Official Title
A Trial of Carboxypeptidase-G2 (CPDG2) and Thymidine for the Management of Patients With Methotrexate Toxicity and Renal Dysfunction
Study Type
Interventional
2. Study Status
Record Verification Date
February 2000
Overall Recruitment Status
Completed
Study Start Date
March 1992 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 2001 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Diseases
Keywords
Antibody, DAMPA, Enzyme, Kidney, Pharmacokinetics, Thymidine, Toxicity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
10 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
carboxypeptidase-G2
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
National Cancer Institute (NCI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
1634927
Citation
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.
Results Reference
background
PubMed Identifier
8625136
Citation
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.
Results Reference
background
PubMed Identifier
9164227
Citation
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.
Results Reference
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Learn more about this trial
A Trial of Carboxypeptidase-G2 (CPDG2) and Thymidine for the Management of Patients With Methotrexate Toxicity and Renal Dysfunction
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