Glucarpidase After High-Dose Methotrexate in Patients With Osteosarcoma
- Conditions
- Osteosarcoma
- Registration Number
- NCT03960177
- Lead Sponsor
- OHSU Knight Cancer Institute
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> - All races and ethnic groups will be eligible<br><br> - A minimum of 6 individuals aged >= 40 years will be enrolled. These<br> participants are considered high-risk.<br><br> - Eastern Cooperative Oncology Group (ECOG) performance score 0-2.<br><br> - Participants must have pathologically confirmed diagnosis of osteosarcoma.<br> Participants must be newly diagnosed and previously untreated, although initiation<br> of doxorubicin/cisplatin prior to enrollment is permitted.<br><br> - Participants must have a recommended treatment plan for their osteosarcoma that<br> includes planned MTX treatment at 8-12 g/m^2.<br><br> - Absolute neutrophil count (ANC) >= 1,000/mm^3 (or >= 1.0 x 10^9/L).<br><br> - Platelet count 75,000/mm^3 (or >= 75 x 10^9/L).<br><br> - Hemoglobin >= 8 g/dL.<br><br> - Serum creatinine =< 1.5 x the upper limit of normal (ULN), or glomerular filtration<br> rate (GFR) >= 60 ml/min/1.73 m^2 as calculated by the Modification of Diet in Renal<br> Disease (MDRD) formula.<br><br> - Total serum bilirubin =< 2 x ULN.<br><br> - Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =< 2.5 x ULN.<br><br> - Participants must be willing to use appropriate contraception for the duration of<br> study treatment and four months after completing HDMTX therapy.<br><br> - Ability to understand and the willingness to sign a written informed consent<br> document.<br><br>Exclusion Criteria:<br><br> - Malignant disease, other than those being treated in this study. Exceptions to this<br> exclusion include the following:<br><br> - Malignancies that were treated curatively and have not recurred within 2 years<br> after completion of treatment;<br><br> - Completely resected basal cell and squamous cell skin cancers;<br><br> - Any malignancy considered to be indolent and that has never required therapy;<br><br> - Completely resected carcinoma in situ of any type.<br><br> - Participants with rapidly progressive disease or organ dysfunction that would<br> prevent them from receiving planned HDMTX treatment regimen.<br><br> - Previous MTX treatment at doses >= 3 g/m^2.<br><br> - Previous treatment with glucarpidase.<br><br> - Known clinically significant liver disease defined as ongoing drug-induced liver<br> injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV),<br> alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis,<br> extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal<br> hypertension, or history of autoimmune hepatitis. Patients who have completed<br> curative therapy for HCV are eligible. Patients with known history of human<br> immunodeficiency virus (HIV) infection are eligible.<br><br> - Participants with a history of hypersensitivity reactions to study agent or its<br> excipients.<br><br> - Participants with a history of hypersensitivity to Escherichia (E.)coli-derived<br> proteins.<br><br> - Participants with large pleural or ascitic fluid collection.<br><br> - Participant is pregnant or breastfeeding, or expecting to conceive or father<br> children within the projected duration of the trial, starting with the screening<br> visit through 120 days after the last dose of trial treatment.<br><br> - Uncontrolled intercurrent illness, or psychiatric illness/social situations that, in<br> the opinion of the investigator, would limit compliance with study requirement,<br> substantially increase risk of incurring AEs or compromise the ability of the<br> patient to give written informed consent.<br><br> - Unable or unwilling to discontinue use of agents that interact significantly with<br> methotrexate metabolism or excretion.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Proportion of subjects completing 4 planned doses of high dose methotrexate (HDMTX)
- Secondary Outcome Measures
Name Time Method Length of hospital stay (LOS) for methotrexate (MTX) clearance;LOS for all causes (excluding MTX-related AEs);Length of hospital stay (LOS) for methotrexate (MTX)-related adverse events (AEs);Percent treatment effect at resection;Incidence of glucarpidase hypersensitivity;Incidence of glucarpidase neutralizing antibodies;Incidence and severity of MTX-related toxicities;Incidence and severity of glucarpidase toxicities;MTX and DAMPA serum concentration (umol/L) at 4, 24, 24.5, 36, 48 and every 24 hours after the start of MTX infusion;Proportion of glucarpidase doses (flat dose) that result in MTX serum concentration reduction of >= 97% from hour 24 to hour 24.5;Proportion of glucarpidase doses (flat dose) that result in 48 hour serum MTX level < 1 uM