Clinical trial NCT03817970: Cisplatin Disposition and Kidney Injury
Official title: Drug Disposition and Nephrotoxicity
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Nephrotoxicity
Keywords: Nephrotoxicity
Cisplatin
Kidney Injury
anti-emetics
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Memorial Sloan Kettering Cancer Center
name: Rutgers University
name: National Institute of General Medical Sciences (NIGMS)
First posted: 2019-01-28
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Kidney Injury with Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel
timeFrame: 3 days
measure: The Effects of 5-HT3 Antagonist Antiemetic Drugs on Cisplatin Secretion
timeFrame: 3 days
Secondary outcomes:
measure: 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
timeFrame: 3 days
Other outcomes:
Locations:
city: Denver
country: United States
facility: UCHealth-Metro Denver
state: Colorado
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: University of Colorado, Denver
name: Melanie Joy, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Edgar Jaimes, MD
role: PRINCIPAL_INVESTIGATOR
References: