CIPN is a common side-effect of anti-neoplastic drugs with no level 1 supportive treatment (Tx) approvals. Management of the adverse event (AE) is restricted to dose reductions and Tx interruptions. GTX is a PSP phycotoxin that reversibly binds voltage-gated sodium channel receptor sites on excitable cells, inhibiting membrane depolarization and nerve impulse conduction. Initial data indicates that GTX (topical formulation) improves PN-symptoms related to anti-HIV drugs. The aim of this study is to evaluate the effect of GTX on sensory symptoms of pts with grade 2 or higher (G≥2) CIPN.
Multicenter trial divided into 2 parts (P1and P2) evaluating the effect of GTX on tactile sensation assessed by Semmens-Weinstein monofilament test (SWMT) on pts with CIPN. P1 is a two-stage, single-arm, open-label study where pts with G≥2 CIPN secondary to taxanes (Cohort 1, C1) and other anti-neoplastic drugs (Cohort 2, C2) are enrolled. The transition to placebo controlled randomized P2 will be determined by the observed efficacy in P1 (minimum 20% response rate in each cohort and overall population). Key exclusion criteria included PN secondary to other causes and ongoing systemic Tx with neurotoxic anti-neoplastic drugs. P1 provides an overall 99.9% power on the primary endpoint. Secondary endpoints included pts reported symptoms and quality of life evaluation.
We report the results of the first stage of P1 where 21 pts were included (C1:11 and C2:10), 60.8% were women with breast or gynecological cancer. All pts had an altered SWMT at baseline, improvement of tactile sensations was seen in 64% in C1 and in 30% in C2. 18,2% had a normal SWMT test after 4 weeks in C1 and 10% in C2, respectively. Overall GTX was well tolerated with no Tx interruption due to AE. At safety visit, 21% pts reported recurrence of PN-related symptoms. 95% of pts reported moderate/severe symptoms at baseline and 62% after 4 weeks of Tx as assessed by patient neuropathy questionnaire (PNQ).
GTX is safe and shows promising activity in the treatment of CIPN, particularly in taxane-treated pts. The primary endpoint for first stage was met, and recruitment in the randomized P2 is ongoing.
Clinical trial identification
NCT05052398 obtained on 21/09/2021.
Legal entity responsible for the study
Has not received any funding.
M.S.F. Dias: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Roche; Financial Interests, Personal, Invited Speaker: Janssen, Astellas, Astellas, AstraZeneca, MSD, Bayer, Amgen, Zodiac; Financial Interests, Personal, travel expenses: AstraZeneca, Janssen, Zodiac; Financial Interests, Institutional, Invited Speaker: Janssen, BMS. F.N. Copati: Non-Financial Interests, Personal, Invited Speaker: Lilly Brazil. M.S. Mano: Non-Financial Interests, Personal, Invited Speaker: Roche, Novartis, Pfizer, MSD, AstraZeneca, Daiichi-Sankyo, MD genomic Health, Lilly; Non-Financial Interests, Personal, Educational Support: Roche, Novartis, Daiichi-Sankyo; Non-Financial Interests, Institutional, Principal Investigator: Roche, Lilly, Novartis; Financial Interests, Personal, Stocks/Shares: Hypera, Grupo Fleury, Qualicorp, Grupo Oncoclinicas. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Servier, Sanofi, Roche, Merck Sharp & Dohme, Libbs, Ipsen, Boehringer Ingelheim, Amgen, Lilly, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Bayer; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck. All other authors have declared no conflicts of interest.