Cisplatin Adverse ReactionNCT05247671
Evaluation of the Effect of Genetic Polymorphisms in ERCC1 and OCT2 on the Occurrence and Severity of Cisplatin-induced Nephrotoxicity
An observational study of Cisplatin Adverse Reaction, run by Ain Shams University at 1 site in Egypt.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cisplatin Adverse Reaction
- What is being tested?
- ERCC1 and OCT2
- How many people
- 89 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Feb 2022to 15 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Faculty of medicine, Ain Shams University
Cairo
Diaa Sherif, MD, 00201221927446, d6.moussa@yahoo.com
About this study
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).
Read the detailed description
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 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 AKI.
Patient written informed consent will be taken prior to study conductance
- Full laboratory evaluation before and after cisplatin administration including: (Complete Blood Count) CBC, liver and renal functions. glomerular filtration rate (GFR), and estimated glomerular filtration rate (eGFR) Serum electrolytes. Marker of nephrotoxicity: Cystatin C.
- Sample Collection and single nucleotide polymorphism (SNP) Genotyping:
Venous blood (2 mL) will be collected from each subject into tubes containing 50 mmol of Ethylenediamine tetraacetic acid (EDTA) per liter and genomic DNA will be isolated with the GeneJET Whole Blood Genomic DNA purification Mini kit, according to manufacturer's instructions. Polymorphisms will be assessed using the TaqMan based real-time polymerase chain reaction (PCR) assay.
This study aims to assess the influence of single nucleotide polymorphisms in the DNA repair gene Excision Repair Cross Complementation group 1 (ERCC1) and Cisplatin uptake transporter gene Organic Cation Transporter 2 (OCT2) on cisplatin-induced nephrotoxicity by assessment of the following:
- Occurrence of nephrotoxicity.
- Degree of renal impairment.
- Changes in traditional and novel protein biomarkers for AKI.
- Conditions
- Cisplatin Adverse Reaction
- Being tested
- ERCC1, OCT2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ERCC1Genetic
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
OCT2Genetic
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: ERCC1; Genetic: OCT2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Creatinine
available in patient profile
Measured: Change from baseline at the end of cycle 1 (each cycle is 28 days)
Serum Creatinine
available in patient profile
Measured: Change from baseline at the end of cycle 2 (each cycle is 28 days)
Secondary outcomes (1)
cystatin c
measured by Human cystatin C ELISA kit
Measured: Change from baseline at the end of cycle 2 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2022
- Study start15 Feb 2022 (estimated)
- Primary completion15 Aug 2022 (estimated)
- Study completion15 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cisplatin Adverse ReactionStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 89 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lamia Elwakeel, Study director, Head of Clinical Department, Faculty of Pharmacy, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05247671
- Sponsor's protocol ID
- PG study on cisplatin
- Status last verified
- Nov 2021
- First submitted
- 10 Dec 2021
- Last updated
- 21 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of Genetic Polymorphisms in ERCC1 and OCT2 on the Occurrence and Severity of Cisplatin-induced Nephrotoxicity
- ClinicalTrials.gov ID
- NCT05247671
- Acronym / sponsor ID
- PG study on cisplatin
- Conditions
- Cisplatin Adverse Reaction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 89 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 15 Feb 2022 (estimated)
- Primary completion
- 15 Aug 2022 (estimated)
- Study completion
- 15 Dec 2022 (estimated)
- First posted
- 21 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 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 AKI.
Patient written informed consent will be taken prior to study conductance
- Full laboratory evaluation before and after cisplatin administration including: (Complete Blood Count) CBC, liver and renal functions. glomerular filtration rate (GFR), and estimated glomerular filtration rate (eGFR) Serum electrolytes. Marker of nephrotoxicity: Cystatin C.
- Sample Collection and single nucleotide polymorphism (SNP) Genotyping:
Venous blood (2 mL) will be collected from each subject into tubes containing 50 mmol of Ethylenediamine tetraacetic acid (EDTA) per liter and genomic DNA will be isolated with the GeneJET Whole Blood Genomic DNA purification Mini kit, according to manufacturer's instructions. Polymorphisms will be assessed using the TaqMan based real-time polymerase chain reaction (PCR) assay.
This study aims to assess the influence of single nucleotide polymorphisms in the DNA repair gene Excision Repair Cross Complementation group 1 (ERCC1) and Cisplatin uptake transporter gene Organic Cation Transporter 2 (OCT2) on cisplatin-induced nephrotoxicity by assessment of the following:
- Occurrence of nephrotoxicity.
- Degree of renal impairment.
- Changes in traditional and novel protein biomarkers for AKI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Case | – | Genetic: ERCC1, Genetic: OCT2All 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ERCC1ERCC1 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 | Genetic | Case |
| OCT2OCT2 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 | Genetic | Case |
Primary outcome
Serum Creatinine
Time frame: Change from baseline at the end of cycle 1 (each cycle is 28 days)
available in patient profile
Serum Creatinine
Time frame: Change from baseline at the end of cycle 2 (each cycle is 28 days)
available in patient profile
1 secondary outcome
cystatin c
Time frame: Change from baseline at the end of cycle 2 (each cycle is 28 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lamia Elwakeel study director
Head of Clinical Department, Faculty of Pharmacy, Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cisplatin Adverse Reaction, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Israa Abdelbar, BSc (00201013138111, israa.aly@bue.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Creatinine (time frame: Change from baseline at the end of cycle 1 (each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2022.