A Randomized Controlled Trial to Evaluate the Efficacy and Safety of Etifoxine for the Prevention of Chemotherapy-Induced Peripheral Neuropathy (CIPN) in Patients Receiving Taxane based regimen.

Introduction: Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a major, disabling side effect of cancer treatment, especially with taxanes, and currently, there are no approved drugs for its prevention. This research protocol proposes to study Etifoxine, a non-benzodiazepine anxiolytic, for CIPN prevention, based on promising results in preclinical models. Etifoxine is believed to exert its neuroprotective effects through a dual mechanism: by modulating the GABA-A receptor and by acting as a Translocator Protein (TSPO) ligand to stimulate the synthesis of neurosteroids, which mitigate processes like neuroinflammation and mitochondrial stress, suggesting its potential role beyond anxiety management and justifying its evaluation in this clinical trial.

Aim: To evaluate the efficacy and safety of Etifoxine for the prevention of clinically significant (Grade greater than or equal to 2) CIPN in adult cancer patients scheduled to receive taxane based chemotherapy.

Design and Duration: A randomized, open-label trial with a planned duration of 24 months.

Population: Adult patients with cancer, aged 18 to 75 years, who are scheduled to receive taxane based chemotherapy. Key exclusion criteria include pre-existing neuropathy (including from Diabetes mellitus), chronic alcohol intake, and use of other neuroprotective agents or anxiolytics.

Intervention:

Arm A (Experimental): Etifoxine 50 mg orally three times daily, starting 7 days before the first dose of taxane for 12 weeks.

Arm B (Control): Patients receive standard of care without any additional intervention.

Follow up: After each cycle of chemotherapy for 6 cycles.

Primary Outcome Measure: The incidence of clinically significant CIPN (Grade greater than or equal to 2) as assessed by NCI CTCAE v5.0 at any time during the study.

Secondary Objectives Include:

1. Comparing patient reported neuropathy and functional impact using the Patient Neurotoxicity Questionnaire (PNQ).
2. Comparing anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS).
3. Comparing neuropathic pain intensity using the Numeric Rating Scale (NRS).
4. Evaluating the overall safety and tolerability of Etifoxine.

Sample Size: A total of 110 patients will be recruited (n=55 per arm), accounting for a 10 percent loss to follow up. This is calculated to detect a one third relative risk reduction in the incidence of CIPN.