A Study of the Effects of GC4419 on Radiation Induced Oral Mucositis in Patients With Head/Neck Cancer

NCT02508389 | Completed Phase 2 Results DMC

• 1 other identifier: GT-201
• Study Type: interventional
• Target: 223
• Locations: 3 countries
• Sites: 64

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.

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

Outcome Measures

Primary Outcomes (1)

• Duration (in Days) of Radiation Induced Severe Oral Mucositis (OM) Per World Health Organization (WHO) Criteria

  Assessed from the first determination of ≥Grade 3 OM to the first instance of non-severe OM (≤Grade 2), without a subsequent instance of ≥Grade 3

  From start of Intensity-modulated radiation therapy (IMRT) through 8 weeks follow-up, an average of 15 weeks

Secondary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events

  First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks.

• Number of Participants Who Experience Severe OM

  Minimum of 60 Gy administered to tumor, approximately 30 IMRT fractions, which is estimated to be 6-7 weeks.

• Number of Participants Who Experienced Grade 4 OM From the First IMRT Fraction Through the Last IMRT Fraction

  First dose of IMRT through the completion of IMRT, estimated to be up to 6-7 weeks.

• Number of IMRT Fractions Delivered at Onset of Severe OM

  Onset of Severe OM, estimated to be between first dose of IMRT and 7 weeks.

• Number of Participants Who Experienced Grade 4 Oral Mucocitis (OM) From the First IMRT Fraction Through the Last IMRT Fraction

  Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks.

Study Arms (3)

Low Dose GC4419: 30mg/day

EXPERIMENTAL

30 mg GC4419/day prior to IMRT

Drug: Low Dose GC4419: 30mg/day; Radiation: Intensity-Modulated Radiation Therapy; Drug: Cisplatin

High Dose GC4419: 90mg/day

EXPERIMENTAL

90 mg GC4419/day prior to IMRT

Drug: High Dose GC4419: 90mg/day; Radiation: Intensity-Modulated Radiation Therapy; Drug: Cisplatin

Placebo

PLACEBO COMPARATOR

Placebo daily, prior to IMRT

Drug: Placebo; Radiation: Intensity-Modulated Radiation Therapy; Drug: Cisplatin

Interventions

Low Dose GC4419: 30mg/day DRUG

Low Dose GC4419 will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).

Low Dose GC4419: 30mg/day

High Dose GC4419: 90mg/day DRUG

High Dose GC4419 will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).

High Dose GC4419: 90mg/day

Placebo DRUG

Placebo will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).

Placebo

Intensity-Modulated Radiation Therapy RADIATION

Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks

High Dose GC4419: 90mg/day; Low Dose GC4419: 30mg/day; Placebo

Cisplatin DRUG

Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor

High Dose GC4419: 90mg/day; Low Dose GC4419: 30mg/day; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate hematologic function as indicated by:
• Absolute neutrophil counts (ANC) ≥ 1,500/mm3
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm3
• 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
• Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test
• Serum pregnancy test negative for females of childbearing potential

You may not qualify if:

• Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands
• Metastatic disease (Stage IV C)
• 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)
• Prior induction chemotherapy
• Receiving any approved or investigational anti-cancer agent other than those provided for in this study
• Participation in another clinical trial or use of another investigational agent within 30 days of study entry
• Requirement for significantly modified diet (liquids and/or solids) due to compromised oral/pharyngeal function at baseline
• Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
• 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
• Active infectious disease excluding oral candidiasis
• Presence of oral mucositis (World Health Organization Score ≥ Grade 1) at study entry
• 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)
• Female patients who are pregnant or breastfeeding
• Known allergies or intolerance to cisplatin and similar platinum-containing compounds
• 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

Sponsors & Collaborators

• Galera Therapeutics, Inc.: lead

Study Sites (64)

University of Arizona Cancer Center at Dignity Health St. Joseph's

Phoenix, Arizona, 85004, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Fowler Family Center for Cancer Care

Jonesboro, Arkansas, 72401, United States

Location

University of Arkansas for Medical Sciences- Winthrop P. Rockefeller Cancer Institute

Little Rock, Arkansas, 72205, United States

Location

VA Long Beach Healthcare System

Long Beach, California, 90822, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Clinical Trials and Research Associates, Inc.

Montebello, California, 90604, United States

Location

UC Irvine Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

St. Mary's Regional Cancer Center

Grand Junction, Colorado, 81501, United States

Location

UConn Health School of Dental Medicine

Farmington, Connecticut, 06030, United States

Location

Pasco Pinellas Cancer Center

Holiday, Florida, 34691, United States

Location

Lakeland Regional Health Cancer Center

Lakeland, Florida, 32504, United States

Location

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Sacred Heart Medical Oncology Group

Pensacola, Florida, 32504, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Indianan, Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Department of Radiation Oncology University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Ashland-Bellefonte Cancer Center

Ashland, Kentucky, 41101, United States

Location

University of Kentucky, Albert B. Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

University of Louisville Hospital, James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Tulane Cancer Center

New Orleans, Louisiana, 70112, United States

Location

CHRISTUS Schumpert Cancer Treatment Center

Shreveport, Louisiana, 71101, United States

Location

Baystate Regional Cancer Program

Springfield, Massachusetts, 01199, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Allegiance Health

Jackson, Michigan, 49201, United States

Location

Lake Huron Medical Center

Port Huron, Michigan, 48060, United States

Location

Ellis Fichel Cancer Center, University of Missouri

Columbia, Missouri, 65212, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Renown Cancer Institute

Reno, Nevada, 89502, United States

Location

Hunterdon Hematology Oncology, LLC Hunterdon Regional Cancer Center

Flemington, New Jersey, 08822, United States

Location

Jersey Shore University Medical Center- Hackensack Meridian Health

Neptune City, New Jersey, 07753, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

East Carolina University, Leo W. Jenkins Cancer Center

Greenville, North Carolina, 27834, United States

Location

Marion L. Shepard Cancer Center

Washington, North Carolina, 27889, United States

Location

Wake Forest Health

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University, James Cancer Center

Columbus, Ohio, 43210, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

VA Portland Health Care System

Portland, Oregon, 97239, United States

Location

St. Luke's University Health Network

Easton, Pennsylvania, 18045, United States

Location

Thomas-Jefferson University Hospital-Bodine Center for Cancer Treatment

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny General Hospital, Allegheny Cancer Center

Pittsburgh, Pennsylvania, 15212, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

AnMed Health Cancer Center

Anderson, South Carolina, 29621, United States

Location

Charleston Cancer Center

Charleston, South Carolina, 29406, United States

Location

Spartanburg Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Prairie Lakes Health Care System

Watertown, South Dakota, 57201, United States

Location

Mountain States Health Alliance

Johnson City, Tennessee, 36704, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Texas Oncology

Plano, Texas, 75093, United States

Location

Scott and White Memorial Hospital and Clinic

Temple, Texas, 76508, United States

Location

Hope Cancer Center

Tyler, Texas, 75701, United States

Location

The University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Providence Regional Medical Center

Everett, Washington, 98201, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Cancer Care Northwest

Spokane, Washington, 99216, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Northeast Cancer Centre, Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Jewish General Hospital

Montreal, Quebec, Canada

Location

Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-centre-du-Québec

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Fundación de Investigación

San Juan, PR, 00927, Puerto Rico

Location

Related Publications (2)

• Mapuskar KA, Vasquez Martinez G, Pulliam CF, Petronek MS, Steinbach EJ, Monga V, Furqan M, Jetton JG, Saunders DP, Pearce A, Davidson S, Pitre L, Dunlap NE, Fairbanks R, Lee CM, Mott SL, Bodeker KL, Cl H, Buatti JM, Anderson CM, Beardsley RA, Holmlund JT, Zepeda-Orozco D, Spitz DR, Allen BG. Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients. Redox Biol. 2023 Apr;60:102599. doi: 10.1016/j.redox.2022.102599. Epub 2023 Jan 3.

  PMID: 36640725 DERIVED

• 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.

  PMID: 35724774 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Stomatitis

Interventions

avasopasem manganese; Radiotherapy, Intensity-Modulated; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Kara Terry
• Organization: Galera Therapeutics, Inc.

kterry@galeratx.com

610-725-1500

Study Officials

• Jon T Holmlund, MD

  Chief Medical Officer

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 24, 2015
• Study Start: October 12, 2015
• Primary Completion: September 18, 2017
• Study Completion: August 29, 2019
• Last Updated: September 20, 2021
• Results First Posted: September 20, 2021

Record last verified: 2021-08

Locations

CA (3); US (60); PR (1)