Cisplatin Induced Kidney Toxicity (ACCENT)
A Canadian Study of Cisplatin mEtabolomics and NephroToxicity
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Michael Zappitelli, MD
- Phone Number: 304077 416-813-7654
- Email: michael.zappitelli@sickkids.ca
Study Contact Backup
- Name: Jasmine Lee, MSc
- Phone Number: 309010 416-813-7654
- Email: jasmine.lee@sickkids.ca
Study Locations
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ONT
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London, ONT, Canada, N6A 5W9
- Recruiting
- London Health Sciences Centre
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Contact:
- Kathie Baer, MSc
- Phone Number: 54524 (519) 685-8500
- Email: kathie.baer@lhsc.on.ca
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Contact:
- Robin Sachdeva, PhD
- Email: Robin.Sachdeva@lhsc.on.ca
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Sub-Investigator:
- Sara Kuruvilla, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Adults receiving Cisplatin as part of their cancer therapy
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We are following patients who are receiving Cisplatin as part of their cancer therapy.
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Children receiving Cisplatin as part of their cancer therapy
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We are following patients who are receiving Cisplatin as part of their cancer therapy.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
To identify patterns of metabolites and specific metabolites prior to and shortly after CisP treatment that predict AKI risk and identify the onset of AKI early (discovery cohort).
Time Frame: 8+ years
|
8+ years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
To independently validate our findings and develop a precision medicine algorithm using metabolites to predict patients at high risk for developing CisP AKI (validation cohort).
Time Frame: 8+ years
|
8+ years
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CisP Metabolomics
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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