Evaluation of the Effect of Rosuvastatin on Cisplatin-induced Nephrotoxicity and Ototoxicity

Cisplatin Adverse Reaction Clinical Trial

Official title:

Evaluation of the Effect of Rosuvastatin on Cisplatin-induced Nephrotoxicity and Ototoxicity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04817904
• Other study ID #: S-4-2020
• Status: Recruiting
• Phase: Phase 2
• Start date: November 17, 2020
• Est. completion date: August 2021

Study information

• Verified date: July 2021
• Source: Cairo University
• Contact: Aya T Moustafa, BSc
• Phone: +201022666179
• Email: ayatarek623[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: August 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cisplatin Adverse Reaction

Intervention

Drug:
• Rosuvastatin 10mg
The statin-treated arm will receive Rosuvastatin tablets 10 mg/day starting from the point of cisplatin initiation through the entire duration of therapy

Locations

Country	Name	City	State
Egypt	Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine	Cairo

Sponsors (2)

Lead Sponsor	Collaborator
Cairo University	German University in Cairo

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

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. — View Citation

Fujieda 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. — View Citation

Pabla 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. Review. — View Citation

Seckl 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of cisplatin-induced nephrotoxicity	Increase in serum creatinine by =0.3 mg/dL or 1.5-2 fold increase from baseline	4 months
Secondary	Difference in biological research markers between both arms	Measurement of total antioxidant capacity and malondialdehyde levels	4 months
Secondary	Difference in sensory-neural hearing impairment in both arms	Audiometry assessment	4 months
Secondary	Incidence of electrolyte imbalance in both arms	Reduction in magnesium level ?1.8 mg/dL and potassium level ?3.5 mmol/L	4 months