Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03960177
Other study ID # STUDY00019380
Secondary ID NCI-2019-02257ST
Status Recruiting
Phase Early Phase 1
First received
Last updated
Start date March 27, 2019
Est. completion date June 1, 2026

Study information

Verified date November 2023
Source OHSU Knight Cancer Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

PRIMARY OBJECTIVE: I. To determine the rate of completion of 4 planned high dose methotrexate (HDMTX) doses when glucarpidase is administered after each dose. SECONDARY OBJECTIVES: I. To assess the length of hospital stay (LOS) associated with methotrexate (MTX) clearance following administration of glucarpidase 24 hours after HDMTX. II. To assess the LOS associated with all causes following administration of glucarpidase 24 hours after HDMTX. III. To assess the impact of glucarpidase administration on HDMTX efficacy. IV. To assess the safety and tolerability of 4 doses of HDMTX administered with glucarpidase in an adult osteosarcoma population. V. To assess the efficacy of glucarpidase flat dose of 1,000 units. OUTLINE: Patients receive standard of care HDMTX intravenously (IV) over 4 hours on day 1 of weeks 4, 5, 9, and 10. After 24 and 48 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. After completion of study treatment, patients are followed up for 32 weeks.


Recruitment information / eligibility

Status Recruiting
Enrollment 12
Est. completion date June 1, 2026
Est. primary completion date June 1, 2025
Accepts healthy volunteers No
Gender All
Age group 25 Years and older
Eligibility Inclusion Criteria: - 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. Exclusion Criteria: - Malignant disease, other than those being treated in this study. Exceptions to this exclusion include the following: - 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Glucarpidase
Given IV
Other:
Quality-of-Life Assessment
Ancillary studies

Locations

Country Name City State
United States Mayo Clinic in Florida Jacksonville Florida
United States Memorial Sloan Kettering Cancer Center New York New York
United States University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania
United States OHSU Knight Cancer Institute Portland Oregon
United States Mayo Clinic in Rochester Rochester Minnesota

Sponsors (3)

Lead Sponsor Collaborator
OHSU Knight Cancer Institute BTG International Inc., Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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)
Secondary 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)
Secondary 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)
Secondary Percent treatment effect at resection Defined as an admixture of degenerating wispy osteoid matrix with empty lacunae, necrotic ghost cells, and edematous stroma with loose fibrous tissue. Dense fibrosis or hyalinization or sheets of sclerotic acellular osteoid may also be present. These features are quantified by estimating the percentage of each parameter in each tumor slide and calculating the mean based on the total number of tumor slides examined. The percentage of tumor necrosis or treatment effect will be recorded from each participant's surgical pathology report. From start of surgery until end of surgery
Secondary Incidence of glucarpidase hypersensitivity Will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Will be determined for participants that received at least 1 dose of glucarpidase following an HDMTX infusion. The 95% CI will be reported with the point estimate of toxicity rate. From first dose of glucarpidase until 30 days after last dose of glucarpidase
Secondary Incidence of glucarpidase neutralizing antibodies Will be determined for participants that received at least 1 dose of glucarpidase following an HDMTX infusion. The 95% CI will be reported with the point estimate of toxicity rate. From first dose of glucarpidase to 30 days after last dose of glucarpidase
Secondary Incidence and severity of MTX-related toxicities Will be assessed according to CTCAE v 5.0. Will be determined for participants that received at least 1 dose of glucarpidase following an HDMTX infusion. The 95% CI will be reported with the point estimate of toxicity rate. From start of first planned MTX infusion to 30 days after last dose of MTX
Secondary Incidence and severity of glucarpidase toxicities Will be assessed according to CTCAE v 5.0. Will be determined for participants that received at least 1 dose of glucarpidase following an HDMTX infusion. The 95% CI will be reported with the point estimate of toxicity rate. From first dose of glucarpidase to 30 days after last dose of glucarpidase
Secondary MTX and DAMPA serum concentration (umol/L) at 4, 24, 24.5, 36, 48 and every 24 hours after the start of MTX infusion From start of each planned MTX infusion to time when MTX =< 0.1 uM (for each planned MTX infusion) (up to 15 days)
Secondary Proportion of glucarpidase doses (flat dose) that result in MTX serum concentration reduction of >= 97% from hour 24 to hour 24.5 Will be presented along with 95% confidence intervals. Summary statistics will be reported on the efficacy analysis set with sub-analyses stratified by glucarpidase dose. From first dose of glucarpidase to end of study treatment (week 10)
Secondary Proportion of glucarpidase doses (flat dose) that result in 48 hour serum MTX level < 1 uM Will be presented along with 95% confidence intervals. Summary statistics will be reported on the efficacy analysis set with sub-analyses stratified by glucarpidase dose. From first dose of glucarpidase to end of study treatment (week 10)
See also
  Status Clinical Trial Phase
Completed NCT00026780 - Eligibility Screening for a NCI Pediatric Oncology Branch Research Study
Not yet recruiting NCT05515068 - Registry For Children, Adolescents And Adults With Osteosarcoma And Biologically Related Bone Sarcomas
Completed NCT02383901 - A Retrospective Non-intervention Study to Characterize FOlate Rescue Treatment in Osteosarcoma Patients Treated With HDMTX N/A
Active, not recruiting NCT01758666 - A Clinical Research on the Relation of Blood Drug Concentration and Calcium Folinate Rescued in High-dose MTX Therapy N/A
Completed NCT01674101 - Effects of Preoperative Physical Therapy in Patients With Lower Extremity Malignancy N/A
Completed NCT01615640 - Diffusion Study on Patients With Osteosarcoma
Completed NCT00520936 - A Study of Pemetrexed in Children With Recurrent Cancer Phase 2
Completed NCT00523419 - Chemotherapy for Patients With Osteosarcoma Phase 2
Completed NCT00132158 - ZD1839 and Oral Irinotecan in Treating Young Patients With Refractory Solid Tumors Phase 1
Not yet recruiting NCT04319874 - Phase II Clinical Trial Scheme of Ganoderma Lucidum Spore Powder for Postoperative Chemotherapy of Osteosarcoma Phase 2
Recruiting NCT06029218 - Analysis of the Toxicity and Efficacy of Daily 1 vs 2 Beam Proton Therapy N/A
Recruiting NCT05642455 - SPEARHEAD-3 Pediatric Study Phase 1/Phase 2
Recruiting NCT06117878 - Safety and Efficacy of NK510 to Treat Osteosarcoma and Soft Tissue Sarcoma Early Phase 1
Not yet recruiting NCT04316091 - A Phase I Clinical Trial of Neoadjuvant Chemotherapy With/Without SPIONs/SMF for Patients With Osteosarcoma Phase 1
Recruiting NCT03932058 - Proteomics Research of Osteosarcoma
Withdrawn NCT01236586 - RO4929097 in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia Phase 1
Completed NCT00743496 - A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma Phase 1
Recruiting NCT04040205 - Abemaciclib for Bone and Soft Tissue Sarcoma With Cyclin-Dependent Kinase (CDK) Pathway Alteration Phase 2
Recruiting NCT05970497 - A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors Phase 1
Active, not recruiting NCT03628209 - Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma Phase 1/Phase 2