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

Study Overview
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Brief Summary
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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

Detailed Description
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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)

Official Title
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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

Conditions
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Chemotherapy-induced Peripheral Neuropathy

Intervention / Treatment
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* Drug: N Acetylcysteine A
* Drug: N Acetylcysteine B


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) |