Clinical trial NCT06553157: Statins Effect on Incidence of Side Effects of Platinum Based Chemotherapy
Official title: Evaluation of the Effect of Statins on the Incidence of Side Effects of Platinum Based Chemotherapy in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Ototoxicity
Keywords: platinum based chemotherapy
Cisplatin
adverse effects
ototoxicity
statins
Lead sponsor: Minia University
Sponsor class: OTHER
First posted: 2024-08-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Platinum based chemotherapy (mainly Cisplatin) is known to cause a variety of adverse effects, including Ototoxicity and nephrotoxicity. Ototoxicity is estimated to affect about 36% of adult patients treated with cisplatin, many therapeutic interventions have been studied to reduce the risk of developing ototoxicity from Cisplatin treatment, Statins have been studied in animals and have shown promising results, this study is aimed to explore the effect of statins on the incidence of ototoxicity in humans.

Detailed description: Cisplatin and other platinum salt agents, including carboplatin and oxaliplatin, are widely used chemotherapy agents in patients with solid malignancies. These agents remain the backbone of treatment for ovarian, cervical, testicular, non-small-cell lung, bladder, and head and neck cancers. It is estimated that more than 500,000 patients diagnosed with these cancers annually in the United States could be candidates for treatment with cisplatin. However, adverse effects such as ototoxicity, neurotoxicity, and nephrotoxicity can sometimes limit their use. The incidence of ototoxicity induced by cisplatin has been estimated to be 36% of adult patients with cancer and 40%-60% of pediatric patients. Ototoxicity can be vestibular or cochlear toxicity or both, which can manifest as tinnitus (ringing in the ear), ear pain, and frank hearing loss.

The receipt of cisplatin is associated with a 5-fold increase in the risk of hearing impairment, and the incidence and severity are cumulative with exposure. Ototoxicity can manifest as tinnitus, hearing loss in the high-frequency range (4,000 to 8,000 Hz), or at late stages, a decreased ability to hear in the lower-frequency normal conversation range. It can occur during or after treatment and can be unilateral or bilateral affect both ears. Usually, hearing loss can start at higher frequencies in the beginning and can be permanent. In fact, severe ototoxicity with deafness has been reported even after a single cycle of cisplatin. Hence, monitoring and early identification of cisplatin-induced hearing loss are crucial to prevent detrimental impact on hearing and thereby the quality of life (QoL). Children affected by hearing loss have a poorer QoL as evident from their ability to communicate and interact with family and peers, their independence, and emotional well-being.The negative impact of hearing impairment on the patients' health-related QoL including social isolation, anxiety, and depression is well supported by a large body of evidence.

In the literature, two studies were found exploring the effect of statins on the incidence of ototoxicity induced by cisplatin, one retrospective study found that patients who used statins concurrently with their cisplatin chemotherapy had a lower incidence of developing ototoxicity, similar results were proven by a study conducted on mice that found that lovastatin protects against development of ototoxicity resulting from cisplatin therapy , a randomized controlled trial exploring the effect of statins on ototoxicity is needed.

Eligibility criteria: Inclusion Criteria:

* Patients will receive platinum based chemotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2.

Exclusion Criteria:

* Pregnant or lactating women.
* Patients receiving vitamin/ supplementation drugs that interfere with the study intervention.
* Patients with contraindications to statins including acute liver failure or decompensated cirrhosis.

Primary outcomes:
measure: change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) using Audiometry as a tool
timeFrame: 3 months after end of treatment
measure: EVALUATION OF THE IMPACT OF HEARING LOSS IN ADULTS (ERSA): Questionnaire
timeFrame: 3 months after end of treatment
Secondary outcomes:
measure: Changes in Otoacoustic emission (OAE): hearing test
timeFrame: 3 months after end of treatment
Other outcomes:
Locations:
city: Minia
country: Egypt
facility: Minia University hospital, department of oncology and nuclear medicine
city: Minya
country: Egypt
facility: Minia University hospital, department of oncology and nuclear medicine
Study officials:
affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Minia University
name: Noha H. Helmy, Masters
role: PRINCIPAL_INVESTIGATOR
affiliation: Pharmaceutics Department, Faculty of Phramacy, Minia university
name: Fatma M. Mady, Professor
role: STUDY_CHAIR
affiliation: Department of Clinical Oncology, Faculty of Medicine, Minia University
name: Nada H. Ali Sholkami, PhD
role: STUDY_DIRECTOR
affiliation: Deaprtment of Clinical Pharmacy, Faculty of Pharmacy, Minia university
name: Eman M. Sadek, PhD
role: STUDY_DIRECTOR
affiliation: Department of ENT, Audio-Vestibular Unit, Faculty of Medicine,Minia University
name: Dalia F. Mohammed Fahim, PhD
role: STUDY_DIRECTOR
References:
citation: Fernandez K, Spielbauer KK, Rusheen A, Wang L, Baker TG, Eyles S, Cunningham LL. Lovastatin protects against cisplatin-induced hearing loss in mice. Hear Res. 2020 Apr;389:107905. doi: 10.1016/j.heares.2020.107905. Epub 2020 Feb 6.
citation: Fernandez KA, Allen P, Campbell M, Page B, Townes T, Li CM, Cheng H, Garrett J, Mulquin M, Clements A, Mulford D, Ortiz C, Brewer C, Dubno JR, Newlands S, Schmitt NC, Cunningham LL. Atorvastatin is associated with reduced cisplatin-induced hearing loss. J Clin Invest. 2021 Jan 4;131(1):e142616. doi: 10.1172/JCI142616.
citation: Dalton DS, Cruickshanks KJ, Klein BE, Klein R, Wiley TL, Nondahl DM. The impact of hearing loss on quality of life in older adults. Gerontologist. 2003 Oct;43(5):661-8. doi: 10.1093/geront/43.5.661.