Evaluation of the Effect of N-acetylcysteine in Preventing Cisplatin-Induced Toxicities in Cancer Patients

Evaluation of the Effect of N-acetylcysteine in Preventing Cisplatin-Induced Toxicities in Cancer Patients

Study Overview

• Status: Recruiting
• Conditions: Cisplatin Adverse Reaction; Cancer Patients; Cisplatin Ototoxicity; Cisplatin Nephrotoxicity; Cisplatin Induced Peripheral Neuropathy
• Intervention / Treatment: Drug: N acetyl cysteine

Detailed Description

Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, Cisplatin was the first heavy metal compound to be used as an antineoplastic, and since its approval by the FDA in 1978, it is one of the most widely used agents in cancer therapy .

It has been used, sole or combined with other chemotherapeutic agents or even in combination with radiotherapy, in the treatment of several types of cancer, such as cancer of the testicles, ovarian, bladder, lung, head and neck, pancreas, breast, endometrium, esophagus, advanced cervical cancer, lymphomas, metastatic osteosarcomas and melanomas.

The therapeutic effect of cisplatin is significantly increased with dose-escalating, but high-dose therapy is limited by severe toxicities, with nephrotoxicity, neurotoxicity, and ototoxicity being the most important complications. In the case of nephrotoxicity, preventive measures such as saline hydration and osmotic diuresis are employed in clinical practice with minor success.

N-acetylcysteine (NAC) is a thiolic amino acid that has been reported to scavenge free radicals, replenish reduced glutathione (GSH), prevent its depletion, and inhibit lipid peroxidation (LPO). It can also restore the deterioration in the pro-oxidant/antioxidant balance via its metal-chelation activity.

Previous studies suggest that pre-administration of NAC attenuates carboplatin-induced injury in the cochlea of rats. As a GSH prodrug and antioxidant, NAC may ameliorate cochlear damage through a variety of mechanisms, such as providing a substrate for cochlear GSH synthesis, free radical scavenging, and inhibition of cell death pathway activation and necrosis.

To date, no clinical trial has been performed to evaluate the preventive potential of oral 1200 mg N-acetylcysteine on cisplatin-induced ototoxicity, hence this trial is designed to examine its effect on ototoxicity, nephrotoxicity, and neurotoxicity in cancer patients treated with cisplatin

Blood samples will be withdrawn from the study patients after enrollment to evaluate each of the following:

1. Complete blood picture (CBC) every cycle
2. Liver transaminases (AST and ALT) at baseline
3. Serum creatinine and blood urea nitrogen every cycle

Baseline glomerular filtration rate will be calculated according to the Cockcroft-Gault formula:

creatinine clearance (ml/min) = (140-age) x body weight plasma creatinine(mg/dl) x 72 The obtained value was multiplied by 0.85 for women.

• Baseline clinical investigations

  1. Audiometric test at baseline and every 2 cycles) patients will undergo conventional pure-tone audiometry in a soundproof room. The pure-tone thresholds for each ear will be measured at frequencies of 250, 500, 1000, 2000, 4000, and 8000 Hz).( bc cancer)
  2. Common terminology criteria for adverse event (CTCAE) version 4 (BC CANCER)
  3. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale.
• Follow-up and end-of-study evaluation The follow up of the patient will occur at the end of each cycle (after 21 days) and at the end of the study after receiving his or her 4th cycle.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: mahmoud ibrahim, master; Phone Number: 01067803525; Email: mahmoudibrahim9797@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Department of Clinical Oncology and Nuclear Medicine, Ain Shams University Hospitals, Cairo, Egypt.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients are eligible for inclusion if they meet the following criteria:

  • Cancer patients aged >18 years receiving cisplatin-containing chemotherapy.
  • A cisplatin dose starting from 75 mg/m2.
  • Various cancer types.
  • Both males and females.
  • No history of organ transplantation or kidney dialysis.
  • Eastern cooperative oncology group performance (ECOG):0-2

Exclusion Criteria:

• Patients with peripheral neuropathy.
• Preexisting unilateral or bilateral moderate to severe sensorineural hearing loss
• Patients with speech discrimination affection or those who are unable to participate in audiologic evaluation
• Co-administration of ifosfamide with cisplatin, because of the known risk of nephrotoxicity.
• Pregnancy 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 [ULN] and alanine transaminase [ALT] or aspartate transaminase [AST] > 3 times the upper normal limit [ULN] or up to 5.0 upper normal limit [ULN] in the presence of hepatic metastases).
• Inadequate renal function (creatinine > 1.25 times upper normal limit [ULN], creatinine clearance < 50mL/min).
• Serious comorbid systemic disorder incompatible with the study (uncontrolled diabetes mellitus or hypertension, myocardial infarction within the last 6 months).
• Patients diagnosed with kidney cancer.
• Exposure to any nephrotoxic drugs or agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group; a. Group 1 (Control group, N = 30 patients) which will include patients who will receive cisplatin chemotherapy starting from 75mg/m2 for 4 cycles (21-28 days and or fractionated)
Active Comparator: treatment group; b. Group 2 (N = 30 patients) will receive N-acetylcysteine 600 mg twice daily (Acetylcystein ® 600 mg effervescent instant granules sachets, Sedico, Egypt) with cisplatin chemotherapy for 4 cycles (21-28 days and or fractionated)	Drug: N acetyl cysteine; N-acetylcysteine 600 mg twice daily (acetylcystein ® 600 mg effervescent instant granules sachets, Sedico, Egypt)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of cisplatin-induced ototoxicity in the form of hearing loss.	hearing loss will be assessed using audiometry	4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of cisplatin-induced nephrotoxicity.	nephrotoxicity will be assessed using serum creatinine and blood urea nitrogen.	4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated)
The occurrence of cisplatin-induced peripheral neuropathy.	peripheral neuropathy will be assessed using Common terminology criteria for adverse event (CTCAE)	4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated)
The occurrence of cisplatin-induced peripheral neuropathy.	peripheral neuropathy will be assessed using The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale	4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated)
The occurrence of cisplatin-induced peripheral neuropathy.	peripheral neuropathy will be assessed using DouleurNeuropathique 4 Questions ( dn4 questionnaire)	4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated)

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: mahmoud ibrahim, Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cisplatin; N-acetylcysteine; Peripheral neuropathy; Ototoxicity; Nephrotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Nervous System Diseases; Wounds and Injuries; Neuromuscular Diseases; Otorhinolaryngologic Diseases; Ear Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Peripheral Nervous System Diseases; Ototoxicity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: RHDIRB2020110301 REC #250

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No