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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.


ABSTRACT: 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 ? 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 (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. 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.

SUBMITTER: Anderson CM 

PROVIDER: S-EPMC6881100 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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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.

Anderson Carryn M CM   Lee Christopher M CM   Saunders Deborah P DP   Curtis Amarinthia A   Dunlap Neal N   Nangia Chaitali C   Lee Arielle S AS   Gordon Sharon M SM   Kovoor Philip P   Arevalo-Araujo Roberto R   Bar-Ad Voichita V   Peddada Abhinand A   Colvett Kyle K   Miller Douglas D   Jain Anshu K AK   Wheeler James J   Blakaj Dukagjin D   Bonomi Marcelo M   Agarwala Sanjiv S SS   Garg Madhur M   Worden Francis F   Holmlund Jon J   Brill Jeffrey M JM   Downs Matt M   Sonis Stephen T ST   Katz Sanford S   Buatti John M JM  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20191016 34


<h4>Purpose</h4>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).<h4>Patients and methods</h4>A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer  ...[more]

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