TY - JOUR
T1 - 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
AU - Anderson, Carryn M.
AU - Lee, Christopher M.
AU - Saunders, Deborah P.
AU - Curtis, Amarinthia
AU - Dunlap, Neal
AU - Nangia, Chaitali
AU - Lee, Arielle S.
AU - Gordon, Sharon M.
AU - Kovoor, Philip
AU - Arevalo-Araujo, Roberto
AU - Bar-Ad, Voichita
AU - Peddada, Abhinand
AU - Colvett, Kyle
AU - Miller, Douglas
AU - Jain, Anshu K.
AU - Wheeler, James
AU - Blakaj, Dukagjin
AU - Bonomi, Marcelo
AU - Agarwala, Sanjiv S.
AU - Garg, Madhur
AU - Worden, Francis
AU - Holmlund, Jon
AU - Brill, Jeffrey M.
AU - Downs, Matt
AU - Sonis, Stephen T.
AU - Katz, Sanford
AU - Buatti, John M.
N1 - Funding Information:
Sanjiv S. Agarwala, MD, St. Luke’s Cancer Center and Temple University, Easton, PA; Carryn Anderson, MD, University of Iowa, Iowa City, IA; Roberto Arevalo-Araujo, MD, Pasco Pinellas Cancer Center, Holiday, FL; Voichita Bar Ad, MD, Thomas-Jefferson University Hospital, Philadelphia, PA; Maura Barry, MD, The University of Vermont Cancer Center, Burlington, VT; Ariel Birnbaum, MD, Rhode Island Hospital, Providence, RI; Dukagjin Blakaj, MD, PhD, Ohio State University, Columbus, OH; Marcelo Bonomi, MD, Wake Forest Baptist Health, Winston-Salem, NC; Leander Cannick III, MD, Anmed Health Cancer Center, Anderson, SC; Daniel Clayburgh, MD, PhD, VA Portland Health Care, System, Portland, OR; Patrick Cobb, MD, FACP, St Vincent Frontier Cancer Center, Billings, MT; Kevin Collins, MD, JD, Fowler Family Center for Cancer Care, Jonesboro, AR; Kyle Colvett, MD, Mountain States Health Alliance Research Department, Johnson City, TN; Amy Curtis, MD, Spartanburg Medical Center, Spartanburg, SC; Bianca de Souza, MD, Henry Ford Allegiance Health, Jackson, MI; Neal Dunlap, MD, University of Louisville, Louisville, KY; Elizabeth Feldman, MS, DMD, UF Health Cancer Center at Orlando Health, Orlando, FL; Madhu Garg, MD, Montefiore Medical Center, Bronx, NY; Sharon M. Gordon, DDS, MPH, PhD, School of Dental Medicine at East Carolina University, Greenville, NC; Alan Gowan, DO, Scott & White Memorial Hospital and Clinic, Temple, TX; Charles Holladay, MD, Charleston Cancer Center, Charleston, SC; Anshu K. Jain, MD, Ash-land-Bellefonte Cancer Center, Ashland, KY and Yale School of Medicine; Joseph Kelley, MD, PhD, University of Tennessee Medical Center, Knoxville, TN; Vernon King, MD, St Mary’s Regional Cancer Center, Grand Junction, CO; Clint Daniel Kingsley, MD, Ellis Fischel Cancer Center - University of Missouri, Columbia, MO; Philip Kovoor, MD, Texas Oncology, Plano West, Plano, TX; Ganesh Kudva, Henry Ford Allegiance Health, Jackson, MI; Arielle Lee, MD, Tyler Hematology-Oncology, Tyler, TX; Christopher Lee, MD, Cancer Care Northwest, Spokane, WA; Steve P. Lee, MD, PhD, Long Beach Veteran Affairs Healthcare System, Long Beach, CA; Ronald Maggiore, MD, VA Portland Health Care System, Portland, OR; Maria Matsangou, MD, Northwestern University, Chicago, IL; Douglas Miller, MD, Jersey Shore University Medical Center, Neptune, NJ; Rex Mowat, MD, Toledo Clinic Cancer Center, Toledo, OH; Rupali Nabar, MD, UC Irvine Medical Center, Orange, CA; Chaitali Nangia, MD, UC Irvine Medical Center, Orange, CA; Jorge Nieva, MD, USC Norris Cancer Center, Los Angeles, CA; Celine Ord, MD, University of Arizona Cancer Center at Dignity Health St Joseph’s, Phoenix, AZ; Shymal Patel, MD, University of Arizona Cancer Center at Dignity Health St Joseph’s, Phoenix, AZ; Abhinand Peddada, MD, Renown Regional Medical Center, Reno, NV; Mercedes Porosnicu, MD, Wake Forest Baptist Health, Winston-Salem, NC; Waqas Rehman, Hunterdon Hematology Oncology, LLC, Flemington, NJ; Deborah P. Saunders, DND, B.Sc, Northeast Cancer Centre of Health Sciences North Northern Ontario School of Medicine, Sudbury, ON, Canada; Khalil Sultanem, MD, Jewish General Hospital, Montreal, QC, Canada; Michael Trendle, MD, Ellis Fischel Cancer Center - University of Missouri, Columbia, MO; Madhavi Venigalla, MD, Lakeland Regional Cancer Center, Lakeland, FL; Francois Vincent, MD, Centre Intégré Universitaire de Santé et de Services Sociaux de la Mauricie et du Centre du Québec Trois-Rivieres, QC, Canada; James Wheeler, MD, Goshen Center for Cancer Care, Goshen, IN; William Wisbeck, MD, Providence Regional Medical Center, Everett, WA; Francis Worden, MD, University of Michigan, Ann Arbor, MI.
Funding Information:
This randomized, double-blind, placebo-controlled phase IIb trial was sponsored and financially supported by Galera Therapeutics. The protocol was approved by each institution’s institutional review board and was registered at ClinicalTrials.gov identifier: NCT02508389). Investigators obtained written informed consent from each participant. Data were anonymized to protect the patients’ identities.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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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U2 - 10.1200/JCO.19.01507
DO - 10.1200/JCO.19.01507
M3 - Article
C2 - 31618127
AN - SCOPUS:85075814654
VL - 37
SP - 3256
EP - 3265
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 34
ER -