Efficacy of NAC for the Prevention and Relief of PIPN in Women With Ovarian, Tubal, and Peritoneal Cancer

Efficacy of N-acetylcysteine for the Prevention and Relief of Paclitaxel-induced Peripheral Neuropathy in Women With Ovarian, Tubal, and Peritoneal Cancer: an Open-label, Randomized Controlled Trial

Ovarian cancer is third most common gynecologic cancer in Thai woman, treatment including surgery followed by chemotherapy.

Patient usually received paclitaxel every 3 week for 6 cycles, paclitaxel induce peripheral neuropathy is common dose dependent side effect which can disturb quality of life, result in chemotherapy dose reduction or discontinuation leading to poor prognosis and decreased survival Mechanism of PIPN including inflammation, promotion of microtubule polymerization and inhibition of depolymerization, and oxidative stress N-acetylcysteine is acetylated form of l-cysteine, might reduce oxidative stress. NAC can restore glutathione level, which is potent natural antioxidant. NAC might reduce PIPN

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Drug: N Acetylcysteine A; Drug: N Acetylcysteine B

Detailed Description

This study was designed to evaluate the effect of NAC on the incidence and severity of PIPN in woman with ovarian, tubal, and peritoneal cancer who treated with paclitaxel for 3 cycles. (PIPPN is developed after cumulative doses 250 mg/m2 or more) Patient in controlled group, received Paclitaxel only. Patient in intervention group divided to two groups. First group received NAC 2400 mg/day for one week after received Paclitaxel each cycle for 3 cycles. Second group received NAC 2400 mg/day for 9 weeks Evaluate incidence and severity of PIPN before start CMT, and every visit after received CMT each cycle using Common Terminology Criteria for Adverse Event (CTCAE) ver.5, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and Patient Neurotoxicity Questionnaire (PNQ)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wichuda deechanda; Phone Number: 093-1951818; Email: ammwd.wichuda@gmail.com
• Study Contact Backup: Name: Marut Yanaranop; Phone Number: 081-3450015; Email: Marut.y@rsu.ac.th

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female patient aged 18 years old or more with ovarian, tubal, and peritoneal cancer who received Paclitaxel first course after surgery
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Normal laboratory testing
• hemoglobin ≥10 g/dL, leukocyte count ≥ 3,000/mL, absolute neutrophil count ≥1,500/mL, platelet count ≥100,000/mL
• Serum creatinine ≤1.5 mg/dL
• Bilirubin ≤1.5 upper limit of normal
• Alkaline phosphatase and serum glutamic oxaloacetate transaminase ≤3 upper limit of normal

Exclusion Criteria:

• Patient with symptoms of peripheral neuropathy before study
• Allergy to N-acetylcysteine
• Psychiatric disorders
• Pregnant woman
• History of treated with other chemotherapy or radiotherapy before study

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC short course; patient received CMT(Paclitaxel) and NAC 2400 mg/day one week per each cycle of CMT	Drug: N Acetylcysteine A; paclitaxel + N-Acetylcysteine orally short course
Experimental: NAC long course; patient received CMT(Paclitaxel) and NAC 2400 mg/day every day for 9 weeks	Drug: N Acetylcysteine B; paclitaxel +N Acetylcysteine orally long course
No Intervention: control; patient received CMT(Paclitaxel) only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paclitaxel-induce peripheral neuropathy	Assessment of grade of peripheral neuropathy by CTCAE v.5.0	Day 0 (before chemotherapy administration), at the end of cycle 1, at the end of cycle 2, and at the end of cycle 3 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of paclitaxel-induce peripheral neuropathy	Assessment of severity of peripheral neuropathy by Patient Neurotoxicity Questionnaire (PNQ)	Day 0 (before chemotherapy administration), at the end of cycle 1, at the end of cycle 2, and at the end of cycle 3 (each cycle is 21 days)
Quality of life associated paclitaxel-induce peripheral neuropathy	Assessment of quality of life using FACT/GOG-Ntx	Day 0 (before chemotherapy administration), at the end of cycle 1, at the end of cycle 2, and at the end of cycle 3 (each cycle is 21 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects of NAC	Nausea, vomiting, diarrhea, abdominal discomfort, allergy	At the end of cycle 1, at the end of cycle 2, and at the end of cycle 3 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Rajavithi Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: July 27, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; 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: 65068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No