Cisplatin Adverse ReactionPhase 2NCT04817904
Evaluation of the Effect of Rosuvastatin on Cisplatin-induced Nephrotoxicity and Ototoxicity
A Phase 2 study testing Rosuvastatin 10mg in people with Cisplatin Adverse Reaction, run by Cairo University at 1 site in Egypt.
Trial summary
Cisplatin is an effective anti-cancer drug for the treatment of many solid tumors in humans. Although the clinical response to cisplatin chemotherapy is encouraging, the nephrotoxicity and ototoxicity of the drug makes it difficult to continue its administration in many cases. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cisplatin Adverse Reaction
- What is being tested?
- Rosuvastatin 10mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteEgypt
- Study dates
- 17 Nov 2020to Aug 2021
- Phase
- Phase 2
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven lung and breast cancer patients indicated for cisplatin (4-6 cycles)
- Normal baseline serum creatinine levels
- Normal baseline audiometry
- Age between 18-70 years
Who cannot join
- Patients with more than one type of cancer
- Patients with prior chemotherapy treatment
- Treatment with statins within 12 months before assignment
- Treatment with fibrates within 4 weeks before assignment
- Pregnancy and Lactation
- Abnormal liver function tests or blood count
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine
Cairo
Loay Kassem, PhD, +201003022907, loay.kassem@cairocure.com
Loay Kassem, PhD
About this study
Cisplatin is an effective anti-cancer drug for the treatment of many solid tumors in humans. Although the clinical response to cisplatin chemotherapy is encouraging, the nephrotoxicity and ototoxicity of the drug makes it difficult to continue its administration in many cases.
Cisplatin nephrotoxicity occurs through several mechanisms, mainly through the transport and accumulation of cisplatin into renal epithelial cells, injury to nuclear and mitochondrial DNA, activation of multiple cell death pathways and initiation of inflammatory response. Accordingly, several experimental strategies were developed to prevent this toxicity. For example, drugs that reduced renal cisplatin accumulation such as organic cation transporter 2 (OCT2) and copper transporter (Ctr1) inhibitors, antioxidants, antiapoptotic and anti-inflammatory agents were investigated. However, many of these drugs interfered with the cytotoxic effects of cisplatin.
Statins are agents used for reducing plasma cholesterol through the inhibition of the enzyme 3- hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase. In addition, statins are also proven to have pleiotropic, non-lipid dependent effects. These effects include anti-inflammatory actions and reduction of oxidative stress. Based on animal studies performed, statins have been shown to reduce the nephrotoxic effects of cisplatin in rats. In addition, ongoing clinical trials are aiming to investigate the role of statins in the protection against the ototoxicity of cisplatin as well. Our aim is to assess the protective effect of statins on cisplatin-induced nephrotoxicity and ototoxicity in humans.
- Conditions
- Cisplatin Adverse Reaction
- Being tested
- Rosuvastatin 10mg
- Keywords
- cisplatin, rosuvastatin, nephrotoxicity, ototoxicity
- Medical subject headings
- Ototoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rosuvastatin 10mgDrug
The statin-treated arm will receive Rosuvastatin tablets 10 mg/day starting from the point of cisplatin initiation through the entire duration of therapy
| Study group | Role | What they receive |
|---|---|---|
| Statin-Treated | Experimental | This arm will be receiving:
* Cisplatin along with conventional nephroprotective interventions (IV hydration with 3 liters with electrolyte replacement administered on the same day of cisplatin)
* Rosuvastatin 10 mg/day Receives: Drug: Rosuvastatin 10mg |
| Statin-Free | No intervention | This arm will be receiving: -Cisplatin along with conventional nephroprotective interventions only (IV hydration with 3 liters with electrolyte replacement administered on the same day of cisplatin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of cisplatin-induced nephrotoxicity
Increase in serum creatinine by ≥0.3 mg/dL or 1.5-2 fold increase from baseline
Measured: 4 months
Secondary outcomes (3)
Difference in biological research markers between both arms
Measurement of total antioxidant capacity and malondialdehyde levels
Measured: 4 months
Difference in sensory-neural hearing impairment in both arms
Audiometry assessment
Measured: 4 months
Incidence of electrolyte imbalance in both arms
Reduction in magnesium level ˂1.8 mg/dL and potassium level ˂3.5 mmol/L
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2021
- Study start17 Nov 2020
- Primary completionAug 2021 (estimated)
- Study completionAug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cisplatin Adverse ReactionStudies of the same condition, open and under way.
- More trials run by Cairo 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Collaborators
- German University in Cairo
- Responsible party
- Principal investigator, Aya Tarek Moustafa, Cairo University
- Investigators
- Mohamed H Solayman, PhD, Study chair, German University in CairoLoay Kassem, PhD, Principal investigator, Cairo UniversityDalia S Elhelw, PhD, Principal investigator, German University in CairoAya T Moustafa, BSc, Principal investigator, German University in Cairo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04817904
- Sponsor's protocol ID
- S-4-2020
- Status last verified
- Jul 2021
- First submitted
- 21 Mar 2021
- Last updated
- 28 Jul 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
An Y, Xin H, Yan W, Zhou X. Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice. Exp Toxicol Pathol. 2011 Mar;63(3):215-9. doi: 10.1016/j.etp.2009.12.002. Epub 2010 Jan 8.
PubMed 20060696Fujieda M, Morita T, Naruse K, Hayashi Y, Ishihara M, Yokoyama T, Toma T, Ohta K, Wakiguchi H. Effect of pravastatin on cisplatin-induced nephrotoxicity in rats. Hum Exp Toxicol. 2011 Jul;30(7):603-15. doi: 10.1177/0960327110376551. Epub 2010 Jul 22.
PubMed 20650967Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. doi: 10.1200/JCO.2016.69.7391. Epub 2017 Feb 27.
PubMed 28240967Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008 May;73(9):994-1007. doi: 10.1038/sj.ki.5002786. Epub 2008 Feb 13.
PubMed 18272962
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of Rosuvastatin on Cisplatin-induced Nephrotoxicity and Ototoxicity
- ClinicalTrials.gov ID
- NCT04817904
- Acronym / sponsor ID
- S-4-2020
- Conditions
- Cisplatin Adverse Reaction
- Keywords
- cisplatin, rosuvastatin, nephrotoxicity, ototoxicity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Collaborators
- German University in Cairo
- Study start
- 17 Nov 2020 (actual)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 26 Mar 2021 (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.
Cisplatin is an effective anti-cancer drug for the treatment of many solid tumors in humans. Although the clinical response to cisplatin chemotherapy is encouraging, the nephrotoxicity and ototoxicity of the drug makes it difficult to continue its administration in many cases.
Cisplatin nephrotoxicity occurs through several mechanisms, mainly through the transport and accumulation of cisplatin into renal epithelial cells, injury to nuclear and mitochondrial DNA, activation of multiple cell death pathways and initiation of inflammatory response. Accordingly, several experimental strategies were developed to prevent this toxicity. For example, drugs that reduced renal cisplatin accumulation such as organic cation transporter 2 (OCT2) and copper transporter (Ctr1) inhibitors, antioxidants, antiapoptotic and anti-inflammatory agents were investigated. However, many of these drugs interfered with the cytotoxic effects of cisplatin.
Statins are agents used for reducing plasma cholesterol through the inhibition of the enzyme 3- hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase. In addition, statins are also proven to have pleiotropic, non-lipid dependent effects. These effects include anti-inflammatory actions and reduction of oxidative stress. Based on animal studies performed, statins have been shown to reduce the nephrotoxic effects of cisplatin in rats. In addition, ongoing clinical trials are aiming to investigate the role of statins in the protection against the ototoxicity of cisplatin as well. Our aim is to assess the protective effect of statins on cisplatin-induced nephrotoxicity and ototoxicity in humans.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Statin-Treated | Experimental | Drug: Rosuvastatin 10mgThis arm will be receiving: * Cisplatin along with conventional nephroprotective interventions (IV hydration with 3 liters with electrolyte replacement administered on the same day of cisplatin) * Rosuvastatin 10 mg/day |
| Statin-Free | No intervention | –This arm will be receiving: -Cisplatin along with conventional nephroprotective interventions only (IV hydration with 3 liters with electrolyte replacement administered on the same day of cisplatin) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically proven lung and breast cancer patients indicated for cisplatin (4-6 cycles)
- Normal baseline serum creatinine levels
- Normal baseline audiometry
- Age between 18-70 years
Key exclusion criteria (6 listed)
- Patients with more than one type of cancer
- Patients with prior chemotherapy treatment
- Treatment with statins within 12 months before assignment
- Treatment with fibrates within 4 weeks before assignment
- Pregnancy and Lactation
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 |
|---|---|---|
| Rosuvastatin 10mgThe statin-treated arm will receive Rosuvastatin tablets 10 mg/day starting from the point of cisplatin initiation through the entire duration of therapy | Drug | Statin-Treated |
Primary outcome
Incidence of cisplatin-induced nephrotoxicity
Time frame: 4 months
Increase in serum creatinine by ≥0.3 mg/dL or 1.5-2 fold increase from baseline
3 secondary outcomes
Difference in biological research markers between both arms
Time frame: 4 months
Difference in sensory-neural hearing impairment in both arms
Time frame: 4 months
Incidence of electrolyte imbalance in both arms
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
- Background: PubMed 20060696An Y, Xin H, Yan W, Zhou X. Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice. Exp Toxicol Pathol. 2011 Mar;63(3):215-9. doi: 10.1016/j.etp.2009.12.002. Epub 2010 Jan 8.
- Background: PubMed 20650967Fujieda M, Morita T, Naruse K, Hayashi Y, Ishihara M, Yokoyama T, Toma T, Ohta K, Wakiguchi H. Effect of pravastatin on cisplatin-induced nephrotoxicity in rats. Hum Exp Toxicol. 2011 Jul;30(7):603-15. doi: 10.1177/0960327110376551. Epub 2010 Jul 22.
- Background: PubMed 28240967Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. doi: 10.1200/JCO.2016.69.7391. Epub 2017 Feb 27.
- Background: PubMed 18272962Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008 May;73(9):994-1007. doi: 10.1038/sj.ki.5002786. Epub 2008 Feb 13.
- Individual participant dataSharing planned: No
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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.
Mohamed H Solayman, PhD study chair
German University in Cairo
Loay Kassem, PhD principal investigator
Cairo University
Dalia S Elhelw, PhD principal investigator
German University in Cairo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rosuvastatin 10mg in people with Cisplatin Adverse Reaction, run by Cairo 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 4 inclusion and 6 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 28 Jul 2021. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Aya T Moustafa, BSc (+201022666179, ayatarek623@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of cisplatin-induced nephrotoxicity (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04817904, which also lists 4 linked publications.
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 28 Jul 2021.