ROMAN: Reduction in oral mucositis with avasopasem manganese (GC4419)–Phase III trial in patients receiving chemoradiotherapy for locally advanced, nonmetastatic head and neck cancer.

TPS6596 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs. 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs. 65%) and severity (incidence of Grade 4, 16% vs. 30%). The safety results were acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (>50 Gy to > 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs. post-op). OM by the WHO scale will be assessed twice weekly during RT & weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), & days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Clinical trial information: NCT03689712 .

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Roman: Reduction in oral mucositis with avasopasem manganese (GC4419)—Phase 3 trial in patients receiving chemoradiotherapy for locally-advanced, non-metastatic head and neck cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps6096 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS6096-TPS6096 ◽

Cited By ~ 2

Author(s):

Jon Holmlund ◽

Jeffrey Mark Brill ◽

Christopher M. Lee ◽

Deborah Saunders ◽

Stephen T. Sonis ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Oral Mucositis ◽

Controlled Trial ◽

Locally Advanced ◽

Intensity Modulated Radiotherapy ◽

Open Label ◽

Double Blind ◽

Who Grade

TPS6096 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs 65%) and severity (incidence of Grade 4, 16% vs 30%). The safety profile was acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (>50 Gy to > 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs post-op). OM by the WHO scale will be assessed twice weekly during RT & weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), & days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Supported by Galera Therapeutics, Inc. Clinical trial information: NCT03689712.

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A double-blind, randomized, placebo-controlled trial of l-glutamine for the severe oral mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.6059 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 6059-6059

Author(s):

Takae Tsujimoto ◽

Yoshifumi Yamamoto ◽

Masafumi Wasa ◽

Yukinori Takenaka ◽

Wataru Nakahara ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Oral Mucositis ◽

Controlled Trial ◽

Locally Advanced ◽

Advanced Head ◽

Double Blind ◽

Severe Oral Mucositis

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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

Journal of Clinical Oncology ◽

10.1200/jco.19.01507 ◽

2019 ◽

Vol 37 (34) ◽

pp. 3256-3265 ◽

Cited By ~ 11

Author(s):

Carryn M. Anderson ◽

Christopher M. Lee ◽

Deborah P. Saunders ◽

Amarinthia Curtis ◽

Neal Dunlap ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Oral Mucositis ◽

Phase Iii ◽

Double Blind Trial ◽

Double Blind ◽

Who Grade ◽

Blind Trial ◽

To Receive

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 ( 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.

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Randomized double-blind, placebo-controlled trial evaluating oral glutamine on radiation-induced oral mucositis and dermatitis in head and neck cancer patients

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy329 ◽

2019 ◽

Vol 109 (3) ◽

pp. 606-614 ◽

Cited By ~ 4

Author(s):

Chih-Jen Huang ◽

Ming-Yii Huang ◽

Pen-Tzu Fang ◽

Frank Chen ◽

Yu-Tsang Wang ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Oral Mucositis ◽

University Hospital ◽

Phase Iii ◽

Care Providers ◽

Double Blind ◽

Radiation Induced

ABSTRACT Background Glutamine is the primary fuel for the gastrointestinal epithelium and maintains the mucosal structure. Oncologists frequently encounter oral mucositis, which can cause unplanned breaks in radiotherapy (RT). Objectives The aim of this study was to explore the association between oral glutamine and acute toxicities in patients with head and neck cancer undergoing RT. Methods This was a parallel, double-blind, randomized, placebo-controlled Phase III trial conducted in a university hospital. A central randomization center used computer-generated tables to allocate interventions to 71 patients with stages I–IV head and neck cancers. The patients, care providers, and investigators were blinded to the group assignment. Eligible patients received either oral glutamine (5 g glutamine and 10 g maltodextrin) or placebo (15 g maltodextrin) 3 times daily from 7 d before RT to 14 d after RT. The primary and secondary endpoints were radiation-induced oral mucositis and neck dermatitis, respectively. These were documented in agreement with the National Cancer Institute Common Terminology Criteria for Adverse Events version 3. Results The study included 64 patients (placebo n = 33; glutamine n = 31) who completed RT for the completers’ analysis. Based on multivariate analysis, glutamine had no significant effect on the severity of oral mucositis (OR: 0.3; 95% CI: 0.05, 1.67; P = 0.169). Only the change in body mass index (BMI) was significant in both multivariate completers (OR: 0.41; 95% CI: 0.20, 0.84; P = 0.015) and per-protocol analysis (OR: 0.40; 95% CI: 0.20, 0.83; P = 0.014). No difference was found in the incidence and severity of neck dermatitis between the two arms. Conclusions The decrease in BMI was strongly related to the severity of oral mucositis in the head and neck cancer patients under RT, but not to the use of glutamine. This trial was registered at clinicaltrials.gov as NCT03015077.

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Prophylaxis of Radiation-Associated Mucositis in Conventionally Treated Patients With Head and Neck Cancer: A Double-Blind, Phase III, Randomized, Controlled Trial Evaluating the Clinical Efficacy of an Antimicrobial Lozenge Using a Validated Mucositis Scoring System

Journal of Clinical Oncology ◽

10.1200/jco.2002.05.046 ◽

2002 ◽

Vol 20 (19) ◽

pp. 3956-3963 ◽

Cited By ~ 50

Author(s):

S. El-Sayed ◽

A. Nabid ◽

W. Shelley ◽

J. Hay ◽

J. Balogh ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Clinical Efficacy ◽

Neck Cancer ◽

Scoring System ◽

Controlled Trial ◽

Phase Iii ◽

Double Blind ◽

Almost All ◽

Severe Mucositis

PURPOSE: Mucositis occurs in almost all patients treated with radiotherapy for head and neck cancer. The aim of this multicenter, double-blind, prospective, randomized trial was to evaluate the clinical efficacy of an economically viable antimicrobial lozenge (bacitracin, clotrimazole, and gentamicin [BcoG]) in the alleviation of radiation-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: One hundred thirty-seven eligible patients were randomized to treatment with either antimicrobial lozenge (69 patients) or placebo lozenge (68 patients). The primary end point of the study was the time to development of severe mucositis from the start of radiotherapy. Secondary end points included severity and duration of mucositis, pain measurement, radiation therapy interruption, and quality of life. Mucositis was scored using a validated mucositis scoring system. RESULTS: Toxicity profiles were similar between the two arms of the study. The median time to development of severe mucositis from the start of radiotherapy was 3.61 weeks on BCoG and 3.96 weeks on placebo (P = .61). There were no statistically significant differences between the arms in the extent of severe mucositis as measured by physician, in oral toxicities as recorded by patients, or in radiotherapy delays. CONCLUSION: This study was conducted on the basis of a pilot study that demonstrated the BCoG lozenge to be tolerable and microbiologically efficacious. A validated mucositis scoring system was used. However, in this group of patients treated with conventional radiotherapy, the lozenge did not impact significantly on the severity of mucositis. Whether such a lozenge would be beneficial in treatment situations where rate of severe mucositis is higher (ie, in patients treated with unconventional fractionation or with concomitant chemotherapy) is unknown.

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