A Two-Stage Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Ec-18 in Altering the Severity and Course of Oral Mucositis Secondary to Chemoradiation Therapy for Squamous Cell Cancers of the Head and Neck.

Background: Oral mucositis (OM) remains a significant toxicity of concomitant chemoradiation (CRT) for head and neck cancer (HNC). This trial assessed the safety and efficacy of EC-18, an innate immune response mitigator, in attenuating severe OM (SOM) in HNC patients being treated with CRT.

Methods: This was a two-stage, Phase 2, randomized, double-blind, placebo-controlled, multi-institutional trial. Stage 1 consisted of a blinded parallel group dose-finding safety and tolerability study of 24 subjects in four equally sized groups of EC-18 (500 mg, 1000 mg, or 2000 mg or placebo). Stage 2 randomized subjects (1:1) to receive placebo or 2000 mg of EC-18. Twice-daily dosing was carried out from the first to the last day of radiation (LDRT). Patients were assessed twice weekly. OM scores were assigned centrally using WHO criteria. Adverse events were reported using NCI-CTCAE v4.0 criteria. Tumor response was reported up to 12 months following the LDRT.

Results: Among patients who received a cumulative radiation dose of at least 55 Gy, at least 80% were compliant with the study's drug dosing during the first 28 days of treatment and continued to use the study drug for more than 4 weeks. EC-18 effectively reduced the duration, onset, and incidence of SOM compared to placebo. Opioid use was delayed in EC-18-treated patients. Efficacy was associated with weekly cisplatin use and HPV positivity. No significant differences in AEs were observed between study cohorts.

Conclusions: EC-18 administered orally may be a safe and effective CRT-associated SOM intervention in patients with HNC.