Phase 2, randomized, double-blind trial of EC-18 versus placebo to mitigate the development and time course of oral mucositis from concomitant chemoradiation for head and neck cancer
Journal of Clinical Oncology
; 40(16), 2022.
Article
in English
| EMBASE | ID: covidwho-2009570
ABSTRACT
Background:
Oral mucositis (OM) is a debilitating side effect of concomitant chemoradiotherapy (CRT) for head and neck cancer (HNC). EC-18 may effectively mitigate OM by minimizing the CRT-induced innate immune response. This Phase II, 2-stage trial evaluated safety, tolerability, and efficacy of EC- 18 in reducing the duration, incidence, and trajectory of severe OM (SOM) in HNC patients.Methods:
Patients (n = 105) with pathologically confirmed oral cavity, oropharynx, hypopharynx, or nasopharynx squamous cell cancers who received intensity-modulated radiation therapy (IMRT;with ≥ 55 Gy on ≥ 2 oral sites) and weekly or tri-weekly cisplatin were studied. In Stage 1, 24 patients were randomized (n = 6 per arm) to receive 500, 1000, or 2000 mg of EC-18, or placebo. Following independent Data Safety Monitoring Board review, 81 patients in Stage 2 received EC-18 2000 mg (n = 41) or placebo (n = 40) throughout CRT. WHO OM grade was assessed twice weekly during IMRT and then once weekly for up to 6 weeks post-IMRT. The primary efficacy endpoint was duration of SOM during the active and short-term follow-up (STFU) periods in the compliant per-protocol population (PP). Much of Stage 2 was conducted during peak periods of the COVID-19 pandemic which measurably impacted patient compliance relative to test medication dosing and planned radiation. Consequently, to assess efficacy most accurately, the PP population was analyzed (with at least 4 weeks of study drug dosing, minimum cumulative radiation of 55 Gy, 80% study drug compliance in the first 28 days of dosing, and without using not-allowed-therapy).Results:
Patient demographics and baseline characteristics were balanced between groups. Adverse events (AEs) were comparable amongst cohorts without drug-related severe AEs. In the PP, the median duration of SOM from baseline through STFU was 0 day in the EC-18 group (n = 22) v 13.5 days in the placebo group (n = 20). SOM incidence through STFU (45.5% v 70%) and opioid use (time to onset 32.3 v 26.0 days;and duration 32.8 v 37.5 days) favored EC-18 v placebo. Results of the covariates analyses suggested that EC-18 favorably impacted SOM incidence in patients who experienced SOM treated with weekly low-dose cisplatin (n = 26;37.5% v placebo 70.0%) and HPV+ tumors (n = 29;35.3% v placebo 66.7%;Table). One-year long-term follow-up for tumor outcomes is ongoing.Conclusions:
EC-18 safely mitigated the development and the time course of SOM in CRT-treated HNC patients. In addition, EC-18 may provide substantial benefits to subpopulations of HPV+ HNC patients treated with low dose cisplatin.
cisplatin; opiate; placebo; adult; cancer patient; cancer staging; chemoradiotherapy; clinical trial; comparative effectiveness; conference abstract; controlled study; coronavirus disease 2019; demographics; double blind procedure; drug efficacy; drug safety; drug therapy; drug tolerability; female; follow up; head and neck cancer; human; hypopharynx; incidence; intensity modulated radiation therapy; low drug dose; major clinical study; male; medication compliance; mouth cavity; nasopharynx; oral mucositis; oropharynx; pandemic; phase 2 clinical trial; radiotherapy; randomized controlled trial; squamous cell carcinoma
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
Journal of Clinical Oncology
Year:
2022
Document Type:
Article
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