2. Academic Validation
  3. 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

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

  • J Clin Oncol. 2019 Dec 1;37(34):3256-3265. doi: 10.1200/JCO.19.01507.
Carryn M Anderson 1,  Christopher M Lee 2,  Deborah P Saunders 3,  Amarinthia Curtis 4,  Neal Dunlap 5,  Chaitali Nangia 6,  Arielle S Lee 7,  Sharon M Gordon 8,  Philip Kovoor 9,  Roberto Arevalo-Araujo 10,  Voichita Bar-Ad 11,  Abhinand Peddada 12,  Kyle Colvett 13,  Douglas Miller 14,  Anshu K Jain 15 16,  James Wheeler 17,  Dukagjin Blakaj 18,  Marcelo Bonomi 18,  Sanjiv S Agarwala 19,  Madhur Garg 20,  Francis Worden 21,  Jon Holmlund 22,  Jeffrey M Brill 22,  Matt Downs 23,  Stephen T Sonis 24,  Sanford Katz 25,  John M Buatti 1
Affiliations

Affiliations

  • 1 University of Iowa Hospitals and Clinics, Iowa City, IA.
  • 2 Cancer Care Northwest, Spokane, WA.
  • 3 North East Cancer Centre, Health Sciences North, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
  • 4 Spartanburg Medical Center, Spartanburg, SC.
  • 5 University of Louisville/James Graham Brown Cancer Center, Louisville, KY.
  • 6 University of California Irvine Medical Center, Orange, CA.
  • 7 HOPE Cancer Center of East Texas, Tyler, TX.
  • 8 East Carolina University, Greenville, NC.
  • 9 Texas Oncology, Plano West, Plano, TX.
  • 10 Pasco Pinellas Cancer Center, Holiday, FL.
  • 11 Thomas Jefferson University, Philadelphia, PA.
  • 12 Renown Regional Medical Center, Reno, NV.
  • 13 Mountain States Health Alliance, Johnson City, TN.
  • 14 Jersey Shore University Medical Center, Neptune, NJ.
  • 15 Ashland-Bellefonte Cancer Center, Ashland, KY.
  • 16 Yale School of Medicine, New Haven, CT.
  • 17 Goshen Center for Cancer Care, Goshen, IN.
  • 18 James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH.
  • 19 St Luke's Cancer Center and Temple University, Easton, PA.
  • 20 Montefiore Medical Center, Bronx, NY.
  • 21 University of Michigan, Ann Arbor, MI.
  • 22 Galera Therapeutics, Malvern, PA.
  • 23 Statistics Collaborative, Washington, DC.
  • 24 Primary Endpoint Solutions, Watertown, MA.
  • 25 Willis-Knighton Cancer Center, Shreveport, LA.
PMID: 31618127 DOI: 10.1200/JCO.19.01507
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 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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