Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM).
PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading.
RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (
CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.
Anderson, Carryn M; Lee, Christopher M; Saunders, Deborah P; Curtis, Amarinthia; Dunlap, Neal; Nangia, Chaitali; Lee, Arielle S; Gordon, Sharon M; Kovoor, Philip; Arevalo-Araujo, Roberto; Bar-Ad, Voichita; Peddada, Abhinand; Colvett, Kyle; Miller, Douglas; Jain, Anshu K; Wheeler, James; Blakaj, Dukagjin; Bonomi, Marcelo; Agarwala, Sanjiv S; Garg, Madhur; Worden, Francis; Holmlund, Jon; Brill, Jeffrey M; Downs, Matt; Sonis, Stephen T; Katz, Sanford; and Buatti, John M, "Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer." (2019). Articles, Abstracts, and Reports. 2724.