Clinical trial NCT05899751: Retrospective Registry Study of Patients With Cancer Treated With High-dose Methotrexate
Official title: High-dose Methotrexate Patterns of Use, Clearance, Toxicities, Supportive Care and Outcomes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Kidney Injury
Drug Toxicity
Keywords: Carboxypeptidases
Delayed Methotrexate Clearance
Hematologic Neoplasms
Hyperhydration
Leucovorin
Osteosarcoma
Lead sponsor: BTG International Inc.
Sponsor class: OTHER
Collaborators: name: Resonance Health
First posted: 2023-06-12
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be conducted at approximately 10 European sites where high-dose methotrexate infusions are administered. Sites will be selected to ensure a balanced accrual of children and adults treated with high-dose methotrexate.

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.


Eligibility criteria: 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.

Exclusion Criteria:

* None.

Primary outcomes:
measure: Delayed Elimination of Methotrexate
timeFrame: 0-48 hours from the start of high-dose methotrexate infusion.
measure: Acute Kidney Injury
timeFrame: 0-48 hours from the start of high-dose methotrexate infusion.
measure: Severe Delayed Elimination of Methotrexate
timeFrame: 0-48 hours from the start of high-dose methotrexate infusion.
Secondary outcomes:
measure: Severity of Acute Kidney Injury
timeFrame: 0-48 hours from the start of high-dose methotrexate infusion.
measure: Hospital Length of Stay
timeFrame: Assessed through study completion, up to 2 years after enrollment.
measure: Hospital Readmission
timeFrame: Within 14 days of high-dose methotrexate infusion.
measure: Delay of Subsequent Chemotherapy
timeFrame: Within 14 days of high-dose methotrexate infusion.
measure: Dose Reduction or Omission of Subsequent High-dose Methotrexate Therapy
timeFrame: Within 14 days of high-dose methotrexate infusion.
measure: Event-Free Survival
timeFrame: 3, 5, and 10 years.
measure: Overall Survival
timeFrame: 3, 5, and 10 years.
measure: Glucarpidase-Related Toxicity
timeFrame: 15 minutes post-glucarpidase through discharge.
measure: Methotrexate Clearance after Glucarpidase
timeFrame: 15 minutes post-glucarpidase through discharge.
measure: Serum Creatinine Level
timeFrame: 15 minutes post-glucarpidase through discharge.
measure: Use of Subsequent High-Dose Methotrexate After Glucarpidase
timeFrame: Within 14 days of high-dose methotrexate infusion.
measure: Disease Outcome After Glucarpidase
timeFrame: 3, 5, and 10 years.
measure: Use of Hyperhydration
timeFrame: Assessed at time of hospital discharge.
measure: Use of Leucovorin
timeFrame: Assessed at time of hospital discharge.
measure: Use of Dialysis or Hemofiltration
timeFrame: Assessed at time of hospital discharge.
measure: Use of Oral Methotrexate Binders
timeFrame: Assessed at time of hospital discharge.
measure: Creatinine Clearance
timeFrame: 15 minutes post-glucarpidase through discharge.
measure: Need for Dialysis
timeFrame: 15 minutes post-glucarpidase through discharge.
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille (APHM), La Timone Hospital
city: Monza
country: Italy
facility: University of Milan-Bicocca
city: Barcelona
country: Spain
facility: Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca (VHIR)
city: Barcelona
country: Spain
facility: Fundación Privada Instituto de Investigación Oncológica de Vall d'Hebron (VHIO)
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
Study officials:
affiliation: University of Milano-Bicocca, Pediatric Hematology Oncology Unit MBBM Foundation
name: Carmelo Rizzari, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramsey LB, Balis FM, O'Brien MM, Schmiegelow K, Pauley JL, Bleyer A, Widemann BC, Askenazi D, Bergeron S, Shirali A, Schwartz S, Vinks AA, Heldrup J. Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance. Oncologist. 2018 Jan;23(1):52-61. doi: 10.1634/theoncologist.2017-0243. Epub 2017 Oct 27.
citation: Taylor ZL, Mizuno T, Punt NC, Baskaran B, Navarro Sainz A, Shuman W, Felicelli N, Vinks AA, Heldrup J, Ramsey LB. MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase. Clin Pharmacol Ther. 2020 Sep;108(3):635-643. doi: 10.1002/cpt.1957. Epub 2020 Jul 18.