Retrospective Registry Study of Patients With Cancer Treated With High-dose Methotrexate

Recruiting

• Conditions: Drug Toxicity; Acute Kidney Injury
• Interventions: Drug: High-dose methotrexate; Drug: Glucarpidase

• Registration Number: NCT05899751
• Lead Sponsor: Protherics Medicines Development Limited

Brief Summary

This retrospective observational study will evaluate high-dose methotrexate patterns of use, supportive care measures used during high-dose methotrexate chemotherapy, along with the incidence of delayed elimination of methotrexate, acute kidney injury and any associated impact of delayed elimination of methotrexate on future courses of chemotherapy and disease outcomes in adults and children with cancer.

The study will compare current practice with existing guidelines and best practices to identify potential gaps in the management of high-dose methotrexate administration and delayed elimination of methotrexate. The study will identify variations in practice and outcomes in different study centers, countries, cancer types, patient age groups, by different methotrexate doses and infusion times and different supportive care measures used. The study will also document the proportion of high-dose methotrexate courses in which glucarpidase has been used and any toxicities attributable to the use of glucarpidase.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-01
• Study First Submitted: 2023-04-11
• Status Verified: 2023-06
• Study First Submitted QC: 2023-06-09
• Study First Posted: 2023-06-12
• Last Update Submitted: 2024-05-09
• Last Update Posted: 2024-05-10
• Primary Completion: 2024-08
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• A diagnosis of any cancer from January 1, 2001 to June 30, 2021.
• Receipt of high-dose methotrexate chemotherapy, defined as a dose of 500 mg/m2 of body surface area or higher.
• Medical records available for review.
• Any age; any cancer type.

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Exclusion Criteria

• None.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients Treated With High-dose Methotrexate	High-dose methotrexate	Patients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy.
Patients Treated With High-dose Methotrexate	Glucarpidase	Patients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy.

Primary Outcome Measures

Name	Time	Method
Severe Delayed Elimination of Methotrexate	0-48 hours from the start of high-dose methotrexate infusion.	Incidence of severe delayed elimination of methotrexate after high-dose methotrexate chemotherapy, defined as a methotrexate level ≥2 standard deviations above the population mean at 36, 42, or 48 hours from the start of high-dose methotrexate infusion and with the presence of acute kidney injury of any grade.
Delayed Elimination of Methotrexate	0-48 hours from the start of high-dose methotrexate infusion.	Incidence of delayed elimination of methotrexate after high-dose methotrexate chemotherapy, defined by Ramsey criteria.
Acute Kidney Injury	0-48 hours from the start of high-dose methotrexate infusion.	Incidence of acute kidney injury of any grade after high-dose methotrexate chemotherapy.

Secondary Outcome Measures

Name	Time	Method
Delay of Subsequent Chemotherapy	Within 14 days of high-dose methotrexate infusion.	Occurrence of delays to further blocks of chemotherapy resulting from delayed methotrexate elimination.
Event-Free Survival	3, 5, and 10 years.	"Events" include death, relapse, abandonment, or refusal of treatment.
Disease Outcome After Glucarpidase	3, 5, and 10 years.	Disease outcome after glucarpidase
Use of Hyperhydration	Assessed at time of hospital discharge.	Incidence of the use of hyperhydration supportive care measures during high-dose methotrexate chemotherapy.
Need for Dialysis	15 minutes post-glucarpidase through discharge.	Renal function, as measured by need for dialysis.
Hospital Length of Stay	Assessed through study completion, up to 2 years after enrollment.	Duration of hospitalization.
Severity of Acute Kidney Injury	0-48 hours from the start of high-dose methotrexate infusion.	Severity of occurrences of acute kidney injury using CTCAE v5 criteria.
Overall Survival	3, 5, and 10 years.	All-cause mortality as well as mortality separately due to disease progression or toxicity.
Methotrexate Clearance after Glucarpidase	15 minutes post-glucarpidase through discharge.	MTX levels.
Dose Reduction or Omission of Subsequent High-dose Methotrexate Therapy	Within 14 days of high-dose methotrexate infusion.	Occurrence of dose reduction or omission of high-dose methotrexate from further cycles of chemotherapy resulting from delayed methotrexate elimination.
Use of Leucovorin	Assessed at time of hospital discharge.	Incidence of the use of leucovorin during high-dose methotrexate chemotherapy.
Use of Dialysis or Hemofiltration	Assessed at time of hospital discharge.	Incidence of the use of dialysis or hemofiltration during high-dose methotrexate chemotherapy.
Use of Oral Methotrexate Binders	Assessed at time of hospital discharge.	Incidence of the use of oral methotrexate binders (cholestyramine, activated charcoal) during high-dose methotrexate chemotherapy.
Creatinine Clearance	15 minutes post-glucarpidase through discharge.	Renal function, as measured by creatinine estimate
Hospital Readmission	Within 14 days of high-dose methotrexate infusion.	Incidence of hospital readmission.
Glucarpidase-Related Toxicity	15 minutes post-glucarpidase through discharge.	Occurrence of toxicities associated with glucarpidase, including frequency, severity (using CTCAE v5 criteria) and including documenting any toxicities of grade 3 or higher.
Use of Subsequent High-Dose Methotrexate After Glucarpidase	Within 14 days of high-dose methotrexate infusion.	Occurrence of subsequent high-dose methotrexate chemotherapy cycles given after glucarpidase.
Serum Creatinine Level	15 minutes post-glucarpidase through discharge.	Renal function, as measured by serum creatinine level.

Trial Locations

Locations (5)

Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca (VHIR); 🇪🇸 Barcelona, Spain

Assistance Publique Hôpitaux de Marseille (APHM), La Timone Hospital; 🇫🇷 Marseille, France

Fundación Privada Instituto de Investigación Oncológica de Vall d'Hebron (VHIO); 🇪🇸 Barcelona, Spain

Hospital Universitario Reina Sofía; 🇪🇸 Córdoba, Spain

University of Milan-Bicocca; 🇮🇹 Monza, Italy