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

Sponsor

Protherics Medicines Development Limited (Other)

Overall Status

Recruiting

CT.gov ID

NCT05899751

Collaborator

Resonance Inc (Other)

1,000

Enrollment

Locations

Anticipated Duration (Months)

200

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury Drug Toxicity	Drug: High-dose methotrexate Drug: Glucarpidase

Study Design

Study Type:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Case-Only

Time Perspective:

Retrospective

Official Title:

High-dose Methotrexate Patterns of Use, Clearance, Toxicities, Supportive Care and Outcomes

Actual Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Patients Treated With High-dose Methotrexate Patients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy.	Drug: High-dose methotrexate High-dose methotrexate Drug: Glucarpidase Glucarpidase

Arm

Intervention/Treatment

Patients Treated With High-dose Methotrexate

Patients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy.

Drug: High-dose methotrexate

High-dose methotrexate

Drug: Glucarpidase

Glucarpidase

Outcome Measures

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
Hospital Length of Stay [Assessed through study completion, up to 2 years after enrollment.]
Duration of hospitalization.
Hospital Readmission [Within 14 days of high-dose methotrexate infusion.]
Incidence of hospital readmission.
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.
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.
Event-Free Survival [3, 5, and 10 years.]
"Events" include death, relapse, abandonment, or refusal of treatment.
Overall Survival [3, 5, and 10 years.]
All-cause mortality as well as mortality separately due to disease progression or toxicity.
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.
Methotrexate Clearance after Glucarpidase [15 minutes post-glucarpidase through discharge.]
MTX levels.
Serum Creatinine Level [15 minutes post-glucarpidase through discharge.]
Renal function, as measured by serum creatinine level.
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.
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.
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
Need for Dialysis [15 minutes post-glucarpidase through discharge.]
Renal function, as measured by need for dialysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Assistance Publique Hôpitaux de Marseille (APHM), La Timone Hospital	Marseille	France	13354
2	University of Milan-Bicocca	Monza	Italy	20900
3	Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca (VHIR)	Barcelona	Spain	08035
4	Fundación Privada Instituto de Investigación Oncológica de Vall d'Hebron (VHIO)	Barcelona	Spain	08035
5	Hospital Universitario Reina Sofía	Córdoba	Spain	14004