RATIONALE

Chronic chemotherapy-induced peripheral neuropathy (CIPN) affects 70% of cancer patients, causing neuropathic pain. Duloxetine is the most recommended treatment for CIPN per most guidelines. However, Methadone, an alternative and effective treatment for refractory neuropathic cancer pain has been under-recognized and under-studied in patients with CIPN.

PARTICIPANTS

Adult patients with cancer and life expectancy greater than 12 weeks who have >grade 1 CIPN based on National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0 grading scale lasting ≥3 months beyond chemotherapy completion.

INTERVENTION

A triple-blind, double-dummy randomized controlled trial, participants randomized to either methadone or duloxetine, followed weekly over 5 weeks with dose titration.

OUTCOMES

Primary outcome is the efficacy of methadone versus duloxetine in reducing average pain intensity from baseline to study end. Secondary outcomes include improvements in functional and quality-of-life interference. Exploratory outcomes include proportion of participants achieving ≥30% or ≥50% pain reduction, patient-reported global impression of change, incidence of adverse events, and methadone dose escalation over a 24-week follow up period.

ANTICIPATED IMPACT

This study will determine if methadone is a viable treatment for CIPN; a very common, distressing, and debilitating condition that otherwise has limited treatment options.

CLINICAL TRIAL REGISTRATION

www.clinicaltrials.gov identifier is NCT05786599.