In a phase IIb trial reported in the Journal of Clinical Oncology, Anderson et al found that the superoxide dismutase mimetic GC4419 was effective in reducing the duration, incidence, and severity of severe oral mucositis in patients with head and neck cancer receiving concurrent radiotherapy and cisplatin.
Study Details
The double-blind trial included 223 patients from 44 sites in the United States and Canada with locally advanced oral cavity or oropharynx cancer who were scheduled to be treated with definitive or postoperative intensity-modulated radiotherapy (IMRT). Patients were randomly assigned 1:1:1 to receive GC4419 at 30 mg (n = 73), GC4419 at 90 mg (n = 76), or placebo (n = 74) via 60-minute intravenous infusion prior to each IMRT fraction. IMRT was given in daily 2.0- to 2.2-Gy fractions Monday through Friday to a cumulative dose of 60 to 72 Gy. Cisplatin was given at 80 to 100 mg/m2 every 3 weeks or 30 to 40 mg/m2 weekly.
The primary endpoint was duration of severe oral mucositis, defined as grade 3 or 4 by World Health Organization criteria.
Results
In the group receiving GC4419 at 90 mg (vs placebo), a significant improvement was observed for severe oral mucositis duration during IMRT (median = 1.5 vs 19 days, P = .024)—which reflected, in part, a 34% relative reduction of incidence of mucositis at any time during IMRT (43% vs 65%; nominal P = .009) and a corresponding increase in the number of patients with a severe oral mucositis duration of 0 days.
Significant improvements were also seen with GC4419 at 90 mg vs placebo in terms of incidence of mucositis at any time during IMRT (43% vs 65%, P = .009) and severity of mucositis at any time during IMRT (grade 4 in 16% vs 30%, P = .045). Numeric improvements were observed in the GC4419 at 30 mg group vs placebo in terms of duration (median = 8 days, P = .163), incidence (60%), and severity (grade 4 in 21%) of severe oral mucositis at any time during IMRT.
KEY POINTS
- GC4419 at a dose of 90 mg was associated with reduced duration, incidence, and severity of severe oral mucositis.
- Toxicity was comparable across treatment groups, with no apparent increases in known toxicities of IMRT plus cisplatin being observed in patients receiving GC4419, and no significant GC4419-specific toxicities being observed.
Toxicity
Toxicity was comparable across treatment groups, with no apparent increases in known toxicities of IMRT plus cisplatin being observed in patients receiving GC4419, and no significant GC4419-specific toxicities being observed. Apparent dose-dependent increases for low-grade hypotension (grade 1 or 2 in 18% of GC4419 30 mg group, 23% of GC4419 90 mg group, and 9% of placebo group) and for mild perioral tingling were observed in patients receiving GC4419; these effects were transient, resolving after GC4419 infusion. No increases in grade 3 hypotension (4%, 4%, and 6%, respectively) or grade 3 syncope (4%, 6%, and 4%) were observed.
The investigators concluded, “GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of [severe oral mucositis] duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN) has begun.”
Carryn M. Anderson, MD, of the Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Galera Therapeutics. For full disclosures of the study authors, visit jco.ascopubs.org.
