Glucarpidase After High-Dose Methotrexate in Patients With Osteosarcoma

NCT03960177 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00019380NCI-2019-02257
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This early phase I trial studies how well glucarpidase works in reducing toxicity in patients with osteosarcoma receiving high dose methotrexate treatment. Glucarpidase may reduce the levels of methotrexate in patients' blood and lead to shorter hospitalizations and a reduction in toxicities.

Conditions

Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects completing 4 planned doses of high dose methotrexate (HDMTX)

  Will be estimated with an exact 95% confidence interval (CI).

  Time from first dose of HDMTX to time of last dose of HDMTX (week 10)

Secondary Outcomes (11)

• Length of hospital stay (LOS) for methotrexate (MTX) clearance

  Time of start of MTX administration to time of MTX =< 0.1uM sample collection for each planned MTX infusion (up to 15 days)

• LOS for all causes (excluding MTX-related AEs)

  Date of admission for each planned MTX infusion to date of discharge for each planned MTX infusion (up to 15 days)

• Length of hospital stay (LOS) for methotrexate (MTX)-related adverse events (AEs)

  Date of admission for each planned MTX infusion to date of discharge for each planned MTX infusion (up to 15 days)

• Percent treatment effect at resection

  From start of surgery until end of surgery

• Incidence of glucarpidase hypersensitivity

  From first dose of glucarpidase until 30 days after last dose of glucarpidase

Study Arms (1)

Treatment (glucarpidase)

EXPERIMENTAL

Patients receive standard of care HDMTX IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. After 24 hours after the start of each HDMTX infusion, patients also receive glucarpidase IV over 5 minutes in the absence of disease progression or unacceptable toxicity.

Drug: Glucarpidase; Other: Quality-of-Life Assessment

Interventions

Glucarpidase DRUG

Given IV

Also known as: Acetylaspartylglutamate Dipeptidase, Carboxypeptidase G2, carboxypeptidase-G2, CPDG2, CPG2, Poly(gamma-glutamic Acid) Endohydrolase, Pteroylpolygammaglutamyl Hydrolase, Voraxaze

Treatment (glucarpidase)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (glucarpidase)

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All races and ethnic groups will be eligible
• A minimum of 6 individuals aged \>= 40 years will be enrolled. These participants are considered high-risk.
• Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
• Participants must have pathologically confirmed diagnosis of osteosarcoma. Participants must be newly diagnosed and previously untreated, although initiation of doxorubicin/cisplatin prior to enrollment is permitted.
• Participants must have a recommended treatment plan for their osteosarcoma that includes planned MTX treatment at 8-12 g/m\^2.
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (or \>= 1.0 x 10\^9/L).
• Platelet count 75,000/mm\^3 (or \>= 75 x 10\^9/L).
• Hemoglobin \>= 8 g/dL.
• Serum creatinine =\< 1.5 x the upper limit of normal (ULN), or glomerular filtration rate (GFR) \>= 60 ml/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease (MDRD) formula.
• Total serum bilirubin =\< 2 x ULN.
• Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =\< 2.5 x ULN.
• Participants must be willing to use appropriate contraception for the duration of study treatment and four months after completing HDMTX therapy.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Malignancies that were treated curatively and have not recurred within 2 years after completion of treatment;
• Completely resected basal cell and squamous cell skin cancers;
• Any malignancy considered to be indolent and that has never required therapy;
• Completely resected carcinoma in situ of any type.
• Participants with rapidly progressive disease or organ dysfunction that would prevent them from receiving planned HDMTX treatment regimen.
• Previous MTX treatment at doses \>= 3 g/m\^2.
• Previous treatment with glucarpidase.
• Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis. Patients who have completed curative therapy for HCV are eligible. Patients with known history of human immunodeficiency virus (HIV) infection are eligible.
• Participants with a history of hypersensitivity reactions to study agent or its excipients.
• Participants with a history of hypersensitivity to Escherichia (E.)coli-derived proteins.
• Participants with large pleural or ascitic fluid collection.
• Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
• Uncontrolled intercurrent illness, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• Unable or unwilling to discontinue use of agents that interact significantly with methotrexate metabolism or excretion.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• BTG International Inc.: collaborator
• Oregon Health and Science University: collaborator

Study Sites (3)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

glucarpidase; gamma-Glutamyl Hydrolase

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christopher Ryan

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 22, 2019
• Study Start: March 27, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (3)