Clinical trial NCT02508389: A Study of the Effects of GC4419 on Radiation Induced Oral Mucositis in Patients With Head/Neck Cancer
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial of the Effects of GC4419 on Severe Oral Mucositis in Patients Receiving Cisplatin + Intensity-modulated Radiation Therapy (IMRT) for Locally Advanced Non-Metastatic Squamous Cell Carcinoma (SCC) of the Oral Cavity/Oropharynx
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Radiation Induced Oral Mucositis
Keywords: squamous cell carcinoma of the head and neck
oral cavity
oropharynx
intensity-modulated radiation therapy
chemotherapy
oral mucositis
superoxide dismutase
radioprotection
Lead sponsor: Galera Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-24
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of the phase 2, GT-201 clinical study is to determine if GC4419 administered prior to intensity-modulated radiation therapy (IMRT) reduces the incidence, duration, and severity of radiation induced oral mucositis in patients who have been diagnosed with locally advanced, non-metastatic squamous cell carcinoma of the head and neck.

Detailed description: GT-201 is a randomized, double-blind, placebo-controlled, multi-center study conducted in the U.S. to evaluate GC4419 administered via an intravenous line (IV) for the reduction of incidence, duration, and severity of radiation induced oral mucositis in patients receiving cisplatin plus intensity-modulated radiation therapy for post-operative, or definitive treatment of locally advanced, non-metastatic squamous cell carcinoma of the head and neck, limited to the oral cavity or oropharynx. Patients will be randomized equally to 1 of 3 treatment arms:

Arm A: 30 mg GC4419 per day (60 min IV infusion to complete within 60 minutes prior to IMRT), concurrent with daily fractions of IMRT (2.0 - 2.2 Gy) to a total of 60 - 72 Gy over approximately 7 weeks, plus cisplatin administered 80 - 100 mg/m2 once every three weeks for 3 doses or 30 - 40 mg/m2 once weekly for 6-7 doses (investigator's choice).

Arm B: 90 mg GC4419 per day (60 min IV infusion to complete within 60 minutes prior to IMRT), concurrent with daily fractions of IMRT (2.0 - 2.2 Gy) to a total of 60 - 72 Gy over approximately 7 weeks, plus cisplatin administered 80 - 100 mg/m2 once every three weeks for 3 doses or 30 - 40 mg/m2 once weekly for 6-7 doses (investigator's choice).

Arm C: Placebo daily (60 min IV infusion to complete within 60 minutes prior to IMRT), concurrent with daily fractions of IMRT (2.0 - 2.2 Gy) to a total of 60 - 72 Gy over approximately 7 weeks, plus cisplatin administered 80 - 100 mg/m2 once every three weeks for 3 doses or 30 - 40 mg/m2 once weekly for 6-7 doses (investigator's choice).

Planned radiation fields in all 3 arms must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) with each site receiving a dose of at least 50 Gy.

All patients will be assessed twice weekly for oral mucositis per WHO grading criteria until the completion of IMRT, and once weekly thereafter (if necessary) for 8 weeks, or until oral mucositis resolves to ≤ Grade 1.

Approximately 200 total to ensure that roughly 60 patients per arm receive study drug and complete requirements for primary endpoint analysis, which is defined as patients receiving a minimum cumulative dose of 60 Gy.

Eligibility criteria: Inclusion Criteria:

1. Pathologically-confirmed diagnosis of squamous cell carcinoma of the head and neck, defined as SCC of the oral cavity or oropharynx that will be treated with cisplatin plus concurrent IMRT Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criteria #2 and #3 below are eligible for the trial.
2. Treatment plan to receive a continuous course of IMRT delivered as single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) that are each planned to receive a total of \> 50 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
3. Treatment plan to receive standard cisplatin monotherapy administered either every three weeks (80-100 mg/m2 for 3 doses) or weekly (30-40 mg/m2 for 6-7 doses). The decision on which chemotherapy regimen to use in combination with IMRT and GC4419 will be at the discretion of the investigator.
4. Age 18 years or older
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Adequate hematologic function as indicated by:

   * Absolute neutrophil counts (ANC) ≥ 1,500/mm3
   * Hemoglobin (Hgb) ≥ 9.0 g/dL
   * Platelet count ≥ 100,000/mm3
7. Adequate renal and liver function as indicated by:

   * Serum creatinine acceptable for treatment with cisplatin per institutional guidelines
   * Total bilirubin ≤ 1.5 x upper-normal limit (ULN)
   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
   * Alkaline phosphatase ≤ 2.5 x ULN
8. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test
9. Serum pregnancy test negative for females of childbearing potential
10. Males and females must agree to use effective contraception starting prior to the first day of treatment and continuing for 30 days after the last dose of GC4419
11. Properly obtained written informed consent

Exclusion Criteria:

1. Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands
2. Metastatic disease (Stage IV C)
3. Prior radiotherapy to the region of the study cancer or adjacent anatomical sites or more than 25% of total body marrow-bearing area (potentially interfering with chemotolerance)
4. Prior induction chemotherapy
5. Receiving any approved or investigational anti-cancer agent other than those provided for in this study
6. Participation in another clinical trial or use of another investigational agent within 30 days of study entry
7. Requirement for significantly modified diet (liquids and/or solids) due to compromised oral/pharyngeal function at baseline
8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
9. Malignant tumors other than head and neck cancer (HNC) within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
10. Active infectious disease excluding oral candidiasis
11. Presence of oral mucositis (World Health Organization Score ≥ Grade 1) at study entry
12. Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)
13. Female patients who are pregnant or breastfeeding
14. Known allergies or intolerance to cisplatin and similar platinum-containing compounds
15. Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure

Primary outcomes:
measure: Duration (in Days) of Radiation Induced Severe Oral Mucositis (OM) Per World Health Organization (WHO) Criteria
timeFrame: From start of Intensity-modulated radiation therapy (IMRT) through 8 weeks follow-up, an average of 15 weeks
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks.
measure: Number of Participants Who Experience Severe OM
timeFrame: Minimum of 60 Gy administered to tumor, approximately 30 IMRT fractions, which is estimated to be 6-7 weeks.
measure: Number of Participants Who Experienced Grade 4 OM From the First IMRT Fraction Through the Last IMRT Fraction
timeFrame: First dose of IMRT through the completion of IMRT, estimated to be up to 6-7 weeks.
measure: Number of IMRT Fractions Delivered at Onset of Severe OM
timeFrame: Onset of Severe OM, estimated to be between first dose of IMRT and 7 weeks.
measure: Number of Participants Who Experienced Grade 4 Oral Mucocitis (OM) From the First IMRT Fraction Through the Last IMRT Fraction
timeFrame: Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks.
measure: Number of Participants With Tumor Outcomes Defined as Locoregional Failure, Distant Metastases, Disease Progression and Deaths
timeFrame: Up to 1 year following completion of chemoradiation.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: University of Arizona Cancer Center at Dignity Health St. Joseph's
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Jonesboro
country: United States
facility: Fowler Family Center for Cancer Care
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences- Winthrop P. Rockefeller Cancer Institute
state: Arkansas
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Montebello
country: United States
facility: Clinical Trials and Research Associates, Inc.
state: California
city: Orange
country: United States
facility: UC Irvine Chao Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Grand Junction
country: United States
facility: St. Mary's Regional Cancer Center
state: Colorado
city: Farmington
country: United States
facility: UConn Health School of Dental Medicine
state: Connecticut
city: Holiday
country: United States
facility: Pasco Pinellas Cancer Center
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Health Cancer Center
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Medical Oncology Group
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Goshen
country: United States
facility: University of Indianan, Goshen Center for Cancer Care
state: Indiana
city: Iowa City
country: United States
facility: Department of Radiation Oncology University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ashland
country: United States
facility: Ashland-Bellefonte Cancer Center
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky, Albert B. Chandler Medical Center
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Hospital, James Graham Brown Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Shreveport
country: United States
facility: CHRISTUS Schumpert Cancer Treatment Center
state: Louisiana
city: Springfield
country: United States
facility: Baystate Regional Cancer Program
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Jackson
country: United States
facility: Henry Ford Allegiance Health
state: Michigan
city: Port Huron
country: United States
facility: Lake Huron Medical Center
state: Michigan
city: Columbia
country: United States
facility: Ellis Fichel Cancer Center, University of Missouri
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Reno
country: United States
facility: Renown Cancer Institute
state: Nevada
city: Flemington
country: United States
facility: Hunterdon Hematology Oncology, LLC Hunterdon Regional Cancer Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center- Hackensack Meridian Health
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Greenville
country: United States
facility: East Carolina University, Leo W. Jenkins Cancer Center
state: North Carolina
city: Washington
country: United States
facility: Marion L. Shepard Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Health
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University, James Cancer Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Portland
country: United States
facility: VA Portland Health Care System
state: Oregon
city: Easton
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas-Jefferson University Hospital-Bodine Center for Cancer Treatment
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital, Allegheny Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Charleston
country: United States
facility: Charleston Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Watertown
country: United States
facility: Prairie Lakes Health Care System
state: South Dakota
city: Johnson City
country: United States
facility: Mountain States Health Alliance
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Plano
country: United States
facility: Texas Oncology
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital and Clinic
state: Texas
city: Tyler
country: United States
facility: Hope Cancer Center
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Everett
country: United States
facility: Providence Regional Medical Center
state: Washington
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Sudbury
country: Canada
facility: Northeast Cancer Centre, Health Sciences North
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-centre-du-Québec
state: Quebec
city: San Juan
country: Puerto Rico
facility: Fundación de Investigación
Study officials:
affiliation: Chief Medical Officer
name: Jon T Holmlund, MD
role: STUDY_CHAIR
References:
citation: Anderson CM, Lee CM, Saunders D, Curtis AE, Dunlap NE, Nangia C, Lee AS, Kovoor P, Bar-Ad V, Pedadda AV Jr, Holmlund J, Downs M, Sonis ST. Two-Year Tumor Outcomes of a Phase 2B, Randomized, Double-Blind Trial of Avasopasem Manganese (GC4419) Versus Placebo to Reduce Severe Oral Mucositis Owing to Concurrent Radiation Therapy and Cisplatin for Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):416-421. doi: 10.1016/j.ijrobp.2022.06.063. Epub 2022 Jun 17.