Cisplatin Induced Kidney Toxicity

NCT ID: NCT04442516

Last Updated: 2024-04-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-08-12
• Study Completion Date: 2028-12-31

Brief Summary

Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still widely used as a first line chemotherapy as it is so effective. Nephrotoxicity is one of the most common adverse effects of CisP, occurring in 20-50% of patients. It manifests as acute kidney injury (AKI) typically within the first few days of exposure and is associated with short and long-term morbidity. Furthermore, AKI diagnosis is only possible once kidney damage has progressed to functional impairment, when mitigation strategies are ineffective. Tests that could predict AKI risk pre-emptively or diagnose early-stage AKI before functional loss would be very impactful, affording opportunities for prevention or early intervention to mitigate CisP nephrotoxicity, reduce morbidity and improve health outcomes.

The field of metabolomics seeks to identify patterns of small molecules (metabolites) involved in cell or tissue metabolism related to disease states, or patient factors like lifestyle and genetics. Plasma and urine are ideal for sampling the metabolome, which can identify at-risk patients and reveal disease-related changes earlier than existing diagnostic methods do.

In CisP-treated children and adults from across Canada, we will identify urine and plasma metabolite profiles a) prior to CisP dosing that predict CisP AKI risk, and b) shortly after dosing to identify early-stage nephrotoxicity, before clinical signs of AKI are detectable. Our identified biomarkers will allow individualization of CisP treatment based on the level of nephrotoxicity risk and the design of trials to mitigate the progression and complications of CisP nephrotoxicity.

Conditions

Acute Kidney Injury; Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Adults receiving Cisplatin as part of their cancer therapy

Questionnaire, sampling of blood, urine and saliva

Intervention Type: OTHER

We are following patients who are receiving Cisplatin as part of their cancer therapy.

Children receiving Cisplatin as part of their cancer therapy

Questionnaire, sampling of blood, urine and saliva

Intervention Type: OTHER

We are following patients who are receiving Cisplatin as part of their cancer therapy.

Interventions

Questionnaire, sampling of blood, urine and saliva

We are following patients who are receiving Cisplatin as part of their cancer therapy.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult participants: Initiating treatment with CisP (≥75 mg/m2) for head/neck or lung cancers at one of the Adult participating sites; 18 years of age or older.
• Paediatric participants: Initiating treatment with CisP for any cancer diagnosis at one of the Pediatric participating sites; greater than 3 months of age.
• All participants: Consent to participate in the study.

Exclusion Criteria

• Diagnosis of chronic kidney disease (CKD) at baseline (glomerular filtration rate <60 mL/min/1.73m2, determined by chart review of either formal glomerular filtration rate testing, 24 hour creatinine creatinine clearance of age-appropriate serum creatinine-based estimated glomerular filtration rate equations; past kidney transplant)
• Previous use of any nephrotoxic drugs included on the provided Excluded Nephrotoxic Medications list in the two weeks prior to initiation of CisP treatment
• Previous use of CisP
• Previous radiotherapy (total body irradiation or abdominal radiation only) in the last 1 month prior to study
• Previous hematopoietic stem cell transplant
• Any chronic or acute health condition that the investigator feels would render the patient inappropriate for this study, including but not limited to significant uncontrolled cardiorespiratory, hepatic, infectious, or renal disease at the discretion of the investigator

• Minimum Eligible Age: 3 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

London Health Sciences Centre

OTHER

Sponsor Role: collaborator

Provincial Health Services Authority

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Michael Zappitelli

Clinician Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

London Health Sciences Centre

London, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Michael Zappitelli, MD

Role: CONTACT

michael.zappitelli@sickkids.ca

416-813-7654 ext. 304077

Jasmine Lee, MSc

Role: CONTACT

jasmine.lee@sickkids.ca

416-813-7654 ext. 309010

Facility Contacts

Kathie Baer, MSc

Role: primary

kathie.baer@lhsc.on.ca

(519) 685-8500 ext. 54524

Robin Sachdeva, PhD

Role: backup

Robin.Sachdeva@lhsc.on.ca

References

Jain A, Huang R, Lee J, Jawa N, Lim YJ, Guron M, Abish S, Boutros PC, Brudno M, Carleton B, Cuvelier GDE, Gunaratnam L, Ho C, Adeli K, Kuruvilla S, Lajoie G, Liu G, Nathan PC, Rod Rassekh S, Rieder M, Waikar SS, Welch SA, Weir MA, Winquist E, Wishart DS, Zorzi AP, Blydt-Hansen T, Zappitelli M, Urquhart B. A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol. Can J Kidney Health Dis. 2021 Nov 17;8:20543581211057708. doi: 10.1177/20543581211057708. eCollection 2021.

Reference Type: DERIVED

PMID: 34820133 (View on PubMed)

Other Identifiers

CisP Metabolomics

Identifier Type: -

Identifier Source: org_study_id