Evaluation of the Effect of Genetic Polymorphisms in ERCC1 and OCT2 on the Occurrence and Severity of Cisplatin-induced Nephrotoxicity

NCT05247671 | Unknown DMC FDA Drug FDA Device

• 1 other identifier: PG study on cisplatin
• Study Type: observational
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

Approximately one-third of all patients treated with cisplatin develop renal dysfunction after a single dosage of cisplatin. Germline genetic polymorphisms may cause variations in cisplatin pharmacokinetics and in the ability of epithelial kidney cells to take up cisplatin and repair cisplatin-induced Deoxyribonucleic Acid (DNA) damage. Knowledge concerning which genotypes are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding cisplatin altogether, to prevent Acute Kidney Injury (AKI).

Conditions

Cisplatin Adverse Reaction

Outcome Measures

Primary Outcomes (2)

• Serum Creatinine

  available in patient profile

  Change from baseline at the end of cycle 1 (each cycle is 28 days)

• Serum Creatinine

  available in patient profile

  Change from baseline at the end of cycle 2 (each cycle is 28 days)

Secondary Outcomes (1)

• cystatin c

  Change from baseline at the end of cycle 2 (each cycle is 28 days)

Study Arms (1)

Case

All eligible patients will be recruited to the study and will be assessed for SNPs in both ERCC1 and OCT2 and their association with cisplatin-induced nephrotoxicity through the measurement of cystatin C before taking cisplatin and after receiving the second cycle of cisplatin.

Genetic: ERCC1; Genetic: OCT2

Interventions

ERCC1 GENETIC

ERCC1 is a rate-limiting enzyme in the nucleotide excision repair pathway that is known to repair cisplatin-induced DNA damage. Polymorphisms in ERCC1 are known to affect response to cisplatin treatment. A mechanism explaining the effect of the ERCC1 polymorphism on the kidney may be that the homozygous carriers of this rs3212986 allele might have a greater capacity to repair cisplatin-induced DNA damage in their kidney epithelia, and thus would be more resistant to cisplatin-induced nephrotoxicity

Case

OCT2 GENETIC

OCT2 is expressed on the basolateral membrane of Proximal Tubular Epithelial Cell (PTEC) and plays a central role in cisplatin uptake into tubular cells. Genetic variants in the cisplatin uptake transporter OCT2 showed association with the preservation of kidney function. Patients with the CT genotype in OCT2 polymorphism rs596881 exhibited positive changes in eGFR compared to individuals with the wild type CC genotype

Case

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Males or females aged \>18 years receiving cisplatin-containing chemotherapy presenting to the Department of Oncology, faculty of medicine, Ain Shams University will be assessed for eligibility according to the inclusion \& exclusion criteria.

You may qualify if:

• Males or females aged \>18 years receiving cisplatin-containing chemotherapy.
• A Cisplatin dose starting from 75 mg/m2
• Various cancer types
• No history of organ transplantation or kidney dialysis.
• Patients with normal renal function

You may not qualify if:

• Co-administration of ifosfamide with cisplatin, because of the known risk of nephrotoxicity.
• Pregnant or lactation.
• Infection with the human immunodeficiency virus (HIV).
• Prior administration of cisplatin.
• Intraperitoneal chemotherapy.
• Inadequate liver function (bilirubin \> 1.5 times upper normal limit (UNL) and alanine transaminase (ALT) or aspartate transaminase (AST) \> 3.0 UNL or up to 5.0 UNL in the presence of hepatic metastases).
• Inadequate renal function (creatinine \> 1.25 times UNL, creatinine clearance \< 50 mL/min).
• Serious comorbid systemic disorder incompatible with the study (uncontrolled diabetes mellitus (DM) or hypertension (HTN), myocardial infarction within the last 6 months).
• Patients diagnosed with kidney cancer.
• Exposure to any nephrotoxic drugs or agents.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Faculty of medicine, Ain Shams University

Cairo, Egypt

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood samples

Study Officials

• Lamia Elwakeel

  Head of Clinical Department, Faculty of Pharmacy, Ain Shams University

  STUDY DIRECTOR

Central Study Contacts

Israa Abdelbar, BSc

CONTACT

00201013138111; israa.aly@bue.edu.eg

Amal Elkholy, PhD

CONTACT

01060355448; amalanas9@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2021
• First Posted: February 21, 2022
• Study Start: February 15, 2022
• Primary Completion: August 15, 2022
• Study Completion: December 15, 2022
• Last Updated: February 21, 2022

Record last verified: 2021-11

Locations

EG (1)