Cisplatin Disposition and Kidney Injury
August 6, 2025 updated by: University of Colorado, Denver
Drug Disposition and Nephrotoxicity
This study is being done to determine 1) whether drugs to treat cisplatin-related nausea can influence harm to the kidneys, 2) whether cisplatin levels in the body can influence the risk of harm to the kidneys, and 3) whether a person's genetic make-up can increase or decrease the likelihood of kidney injury due to cisplatin therapy.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
Cisplatin (cis-diamminedichloroplatinum, Platinol®) is commonly utilized in chemotherapy regimens for the treatment of solid cancers including lung, head and neck, and cervix.
Its main mechanism of action is through binding of DNA to form cross-links, leading to arrest of DNA synthesis and replication.
A major adverse consequence of cisplatin therapy is acute kidney injury (AKI).
It is reported that between 30 and 38 percent of patients develop signs of nephrotoxicity (toxicity in the kidneys) after a single cisplatin dose, despite strategies such as hydration to limit renal exposure.
This is problematic for patients as kidney injury can delay further treatment and limit the total number of chemotherapy cycles received, thereby reducing the overall efficacy of cisplatin-containing regimens.
Furthermore, it is apparent that cisplatin will remain a central component to the treatment of solid tumors in the foreseeable future.
New approaches to identify patients at risk of acute kidney injury (AKI) and prevent its development and progression are urgently needed.
Cisplatin causes nausea and vomiting, which requires treatment with 5-HT3 antagonists (5-HT3A) to control.
Associations between the clinical use of the 5-HT3A antiemetic drugs and the risk of cisplatin AKI have recently been discovered.
This study will interrogate relationships between 5-HT3A drugs (granisetron, ondansetron, and palonosetron) and cisplatin AKI.
Study Type
Interventional
Enrollment (Estimated)
72
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Colorado
-
Denver, Colorado, United States, 80045
- UCHealth-Metro Denver
-
-
New York
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Male or female patient prescribed cisplatin at a dose of >25mg/m^2
- Age 18-80 years
- Hemoglobin >/=9 g/dl
- No consumption of grapefruit juice or alcohol within 7 days
- No history of alcohol consumption of >14 drinks/week
- No history of organ transplantation or kidney dialysis
- Willingness to comply with study
- Not pregnant or lactating
- No changes in chronic medications within 2 weeks
- Estimated glomerular filtration rate (eGFR) > 60 ml/min^2
- Normal liver function (ALT and AST <2x ULN)
Exclusion Criteria:
- Diagnosis of kidney cancer
- Previous exposure to platinum-based chemotherapy with the exception of one previous dose as part of the current course
- Herbal supplement use beyond marijuana
- Exposure to other known nephrotoxins (including contrast agents) within the previous 2 weeks
- Severe gastrointestinal disease with fluid losses
- Diagnosis of a rapidly progressive glomerulonephritis
- Allergy or contraindication to 5-HT3 Antagonists
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Granisetron
Participants randomized to an antiemetic regimen containing granisetron 2 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.
|
An antiemetic regimen containing granisetron 2 mg oral or IV.
Other Names:
|
|
Experimental: Ondansetron
Participants randomized to an antiemetic regimen containing ondansetron 8 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.
|
An antiemetic regimen containing ondansetron 8 mg oral or IV.
Other Names:
|
|
Experimental: Palonosetron
Participants randomized to an antiemetic regimen containing palonosetron 0.25 mg IV and evaluated for cisplatin toxicity after the first dose of cisplatin.
|
An antiemetic regimen containing palonosetron 0.25 mg IV.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Kidney Injury with Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel
Time Frame: 3 days
|
The effects of 5-HT3 antagonist antiemetic drugs on cisplatin kidney injury as indicated by a 1.5 fold increase in the urinary biomarker panel values at 3 days after treatment
|
3 days
|
|
The Effects of 5-HT3 Antagonist Antiemetic Drugs on Cisplatin Secretion
Time Frame: 3 days
|
The changes to cisplatin secretion in the urine (as an early biomarker for the detection of kidney injury) as indicated by a 6 mg difference between 5-HT3 Antagonist Antiemetic Drugs at 3 days after treatment
|
3 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Targeted Genetic Polymorphisms are Associated with Risk of Kidney Injury Due to Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel
Time Frame: 3 days
|
The influence of targeted genetic polymorphisms on risk of kidney injury due to cisplatin and 5-HT3 Antagonist Antiemetic Drugs as indicated by a 1.5 fold increase in a urinary biomarker panel values at 3 days after treatment
|
3 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Melanie Joy, PharmD, PhD, University of Colorado, Denver
- Principal Investigator: Edgar Jaimes, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- George B, Joy MS, Aleksunes LM. Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy. Exp Biol Med (Maywood). 2018 Feb;243(3):272-282. doi: 10.1177/1535370217745302. Epub 2017 Dec 12.
- Chang C, Hu Y, Hogan SL, Mercke N, Gomez M, O'Bryant C, Bowles DW, George B, Wen X, Aleksunes LM, Joy MS. Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin. Int J Mol Sci. 2017 Jun 22;18(7):1333. doi: 10.3390/ijms18071333.
- George B, You D, Joy MS, Aleksunes LM. Xenobiotic transporters and kidney injury. Adv Drug Deliv Rev. 2017 Jul 1;116:73-91. doi: 10.1016/j.addr.2017.01.005. Epub 2017 Jan 20.
- George B, Wen X, Mercke N, Gomez M, O'Bryant C, Bowles DW, Hu Y, Hogan SL, Joy MS, Aleksunes LM. Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-dependent Changes in the Absence of Clinical Nephrotoxicity. Clin Pharmacol Ther. 2017 Apr;101(4):510-518. doi: 10.1002/cpt.606. Epub 2017 Feb 14.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 15, 2019
Primary Completion (Estimated)
September 30, 2027
Study Completion (Estimated)
December 31, 2027
Study Registration Dates
First Submitted
November 27, 2018
First Submitted That Met QC Criteria
January 22, 2019
First Posted (Actual)
January 28, 2019
Study Record Updates
Last Update Posted (Actual)
August 11, 2025
Last Update Submitted That Met QC Criteria
August 6, 2025
Last Verified
August 1, 2025
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antiemetics
- Autonomic Agents
- Peripheral Nervous System Agents
- Gastrointestinal Agents
- Dermatologic Agents
- Neurotransmitter Agents
- Antipruritics
- Serotonin 5-HT3 Receptor Antagonists
- Serotonin Antagonists
- Serotonin Agents
- Palonosetron
- Ondansetron
- Granisetron
Other Study ID Numbers
- 18-1752.cc
- R01GM123330 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.