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

NCT ID: NCT02508389

Last Updated: 2021-09-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

223 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-12

Study Completion Date

2019-08-29

Brief Summary

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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

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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.

Conditions

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Radiation Induced Oral Mucositis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Low Dose GC4419: 30mg/day

30 mg GC4419/day prior to IMRT

Group Type EXPERIMENTAL

Low Dose GC4419: 30mg/day

Intervention Type 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).

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

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

Cisplatin

Intervention Type 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

90 mg GC4419/day prior to IMRT

Group Type EXPERIMENTAL

High Dose GC4419: 90mg/day

Intervention Type 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).

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

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

Cisplatin

Intervention Type 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

Placebo

Placebo daily, prior to IMRT

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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).

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

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

Cisplatin

Intervention Type 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

Interventions

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Low Dose GC4419: 30mg/day

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).

Intervention Type DRUG

High Dose GC4419: 90mg/day

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).

Intervention Type DRUG

Placebo

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).

Intervention Type DRUG

Intensity-Modulated Radiation Therapy

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

Intervention Type RADIATION

Cisplatin

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Galera Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jon T Holmlund, MD

Role: STUDY_CHAIR

Chief Medical Officer

Locations

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

Phoenix, Arizona, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

Fowler Family Center for Cancer Care

Jonesboro, Arkansas, United States

Site Status

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

Little Rock, Arkansas, United States

Site Status

VA Long Beach Healthcare System

Long Beach, California, United States

Site Status

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Clinical Trials and Research Associates, Inc.

Montebello, California, United States

Site Status

UC Irvine Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Stanford Cancer Institute

Stanford, California, United States

Site Status

St. Mary's Regional Cancer Center

Grand Junction, Colorado, United States

Site Status

UConn Health School of Dental Medicine

Farmington, Connecticut, United States

Site Status

Pasco Pinellas Cancer Center

Holiday, Florida, United States

Site Status

Lakeland Regional Health Cancer Center

Lakeland, Florida, United States

Site Status

UF Health Cancer Center at Orlando Health

Orlando, Florida, United States

Site Status

Sacred Heart Medical Oncology Group

Pensacola, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Indianan, Goshen Center for Cancer Care

Goshen, Indiana, United States

Site Status

Department of Radiation Oncology University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Ashland-Bellefonte Cancer Center

Ashland, Kentucky, United States

Site Status

University of Kentucky, Albert B. Chandler Medical Center

Lexington, Kentucky, United States

Site Status

University of Louisville Hospital, James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Tulane Cancer Center

New Orleans, Louisiana, United States

Site Status

CHRISTUS Schumpert Cancer Treatment Center

Shreveport, Louisiana, United States

Site Status

Baystate Regional Cancer Program

Springfield, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Henry Ford Allegiance Health

Jackson, Michigan, United States

Site Status

Lake Huron Medical Center

Port Huron, Michigan, United States

Site Status

Ellis Fichel Cancer Center, University of Missouri

Columbia, Missouri, United States

Site Status

Billings Clinic

Billings, Montana, United States

Site Status

St. Vincent Frontier Cancer Center

Billings, Montana, United States

Site Status

Renown Cancer Institute

Reno, Nevada, United States

Site Status

Hunterdon Hematology Oncology, LLC Hunterdon Regional Cancer Center

Flemington, New Jersey, United States

Site Status

Jersey Shore University Medical Center- Hackensack Meridian Health

Neptune City, New Jersey, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

East Carolina University, Leo W. Jenkins Cancer Center

Greenville, North Carolina, United States

Site Status

Marion L. Shepard Cancer Center

Washington, North Carolina, United States

Site Status

Wake Forest Health

Winston-Salem, North Carolina, United States

Site Status

Ohio State University, James Cancer Center

Columbus, Ohio, United States

Site Status

Toledo Clinic Cancer Center

Toledo, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

VA Portland Health Care System

Portland, Oregon, United States

Site Status

St. Luke's University Health Network

Easton, Pennsylvania, United States

Site Status

Thomas-Jefferson University Hospital-Bodine Center for Cancer Treatment

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital, Allegheny Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

AnMed Health Cancer Center

Anderson, South Carolina, United States

Site Status

Charleston Cancer Center

Charleston, South Carolina, United States

Site Status

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Site Status

Prairie Lakes Health Care System

Watertown, South Dakota, United States

Site Status

Mountain States Health Alliance

Johnson City, Tennessee, United States

Site Status

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Site Status

Texas Oncology

Plano, Texas, United States

Site Status

Scott and White Memorial Hospital and Clinic

Temple, Texas, United States

Site Status

Hope Cancer Center

Tyler, Texas, United States

Site Status

The University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

Providence Regional Medical Center

Everett, Washington, United States

Site Status

VA Puget Sound Health Care System

Seattle, Washington, United States

Site Status

Cancer Care Northwest

Spokane, Washington, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Northeast Cancer Centre, Health Sciences North

Greater Sudbury, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

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

Trois-Rivières, Quebec, Canada

Site Status

Fundación de Investigación

San Juan, PR, Puerto Rico

Site Status

Countries

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United States Canada Puerto Rico

References

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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.

Reference Type DERIVED
PMID: 36640725 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35724774 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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GT-201

Identifier Type: -

Identifier Source: org_study_id

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