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

NCT04817904 | Unknown Phase 2 FDA Drug

• 1 other identifier: S-4-2020
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cisplatin Adverse Reaction

Keywords

cisplatin; rosuvastatin; nephrotoxicity; ototoxicity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Difference in biological research markers between both arms

  4 months

• Difference in sensory-neural hearing impairment in both arms

  4 months

• Incidence of electrolyte imbalance in both arms

  4 months

Study Arms (2)

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

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)

Interventions

Rosuvastatin 10mg DRUG

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

Statin-Treated

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cairo University: lead
• German University in Cairo: collaborator

Study Sites (1)

Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine

Cairo, Egypt

RECRUITING

Related 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.

  PMID: 20060696 BACKGROUND

• 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.

  PMID: 20650967 BACKGROUND

• 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.

  PMID: 28240967 BACKGROUND

• 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.

  PMID: 18272962 BACKGROUND

MeSH Terms

Conditions

Ototoxicity

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Ear Diseases; Otorhinolaryngologic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mohamed H Solayman, PhD

  German University in Cairo

  STUDY CHAIR

• Loay Kassem, PhD

  Cairo University

  PRINCIPAL INVESTIGATOR

• Dalia S Elhelw, PhD

  German University in Cairo

  PRINCIPAL INVESTIGATOR

• Aya T Moustafa, BSc

  German University in Cairo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aya T Moustafa, BSc

CONTACT

+201022666179; ayatarek623@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 21, 2021
• First Posted: March 26, 2021
• Study Start: November 17, 2020
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)