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Cisplatin Disposition and Kidney Injury

Sponsor
University of Colorado, Denver (Other)
Overall Status
Recruiting
CT.gov ID
NCT03817970
Collaborator
Memorial Sloan Kettering Cancer Center (Other), Rutgers University (Other), National Institute of General Medical Sciences (NIGMS) (NIH)
72
Enrollment
2
Locations
3
Arms
42.2
Anticipated Duration (Months)
36
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
72 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Drug Disposition and Nephrotoxicity
Actual Study Start Date :
Jun 26, 2019
Anticipated Primary Completion Date :
Sep 30, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

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.

Drug: Granisetron
An antiemetic regimen containing granisetron 2 mg oral or IV.
Other Names:
  • Kytril

    		•
    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.

    Drug: Ondansetron
    An antiemetic regimen containing ondansetron 8 mg oral or IV.
    Other Names:
  • Zofran

    		•
    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.

    Drug: Palonosetron
    An antiemetic regimen containing palonosetron 0.25 mg IV.
    Other Names:
  • Aloxi

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Kidney Injury with Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel [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

    2. The Effects of 5-HT3 Antagonist Antiemetic Drugs on Cisplatin Secretion [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

    Secondary Outcome Measures

    1. 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 [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female patient prescribed cisplatin at a dose of >25 mg/m^2

    • Age 18-80 years

    • Hemoglobin >/=10 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

    • Herbal supplement use beyond marijuana

    • Exposure to other known nephrotoxins (including contrast agents) within the previous 2 weeks

    • Concurrent use of competitive inhibitors of transport proteins (metformin, cimetidine, ranitidine, antiviral drugs, cephalosporins, topotecan, methotrexate, vinblastine)

    • Severe gastrointestinal disease with fluid losses

    • Diagnosis of a rapidly progressive glomerulonephritis

    • Allergy or contraindication to 5-HT3 Antagonists

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCHealth-Metro Denver Denver Colorado United States 80045
    2 Memorial Sloan Kettering Cancer Center New York New York United States 10065

    Sponsors and Collaborators

    • University of Colorado, Denver
    • Memorial Sloan Kettering Cancer Center
    • Rutgers University
    • National Institute of General Medical Sciences (NIGMS)

    Investigators

    • Principal Investigator: Lauren Aleksunes, PharmD, PhD, Rutgers University
    • Principal Investigator: Melanie Joy, PharmD, PhD, University of Colorado, Denver

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University of Colorado, Denver
    ClinicalTrials.gov Identifier:
    NCT03817970
    Other Study ID Numbers:
    • 18-1752.cc
    • 1R01GM123330-01A1
    First Posted:
    Jan 28, 2019
    Last Update Posted:
    Sep 29, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by University of Colorado, Denver
    Nephrotoxicity
    Cisplatin
    Kidney Injury
    anti-emetics
    Additional relevant MeSH terms:
    Ondansetron
    Palonosetron
    Granisetron

    Study Results

    No Results Posted as of Sep 29, 2021