Radiation Induced Oral MucositisPhase 2NCT02508389
A Study of the Effects of GC4419 on Radiation Induced Oral Mucositis in Patients With Head/Neck Cancer
A Phase 2 study testing Low Dose GC4419: 30mg/day, High Dose GC4419: 90mg/day and Intensity-Modulated Radiation Therapy in people with Radiation Induced Oral Mucositis, run by Galera Therapeutics, Inc. at 64 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Radiation Induced Oral Mucositis
- What is being tested?
- Low Dose GC4419: 30mg/day, High Dose GC4419: 90mg/day and Intensity-Modulated Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 223 participants
- Where
- 64 sitesin 3 countries
- Study dates
- 12 Oct 2015to 29 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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:
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- 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
- 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
- Properly obtained written informed consent
Who cannot join
- 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
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- 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
Trial locations and contacts
64 sites in 3 countries.
64 sites in 3 countries
United States60 sites
AnMed Health Cancer Center
Anderson, South Carolina, 29621
University of Michigan
Ann Arbor, Michigan, 48109
Ashland-Bellefonte Cancer Center
Ashland, Kentucky, 41101
Billings Clinic
Billings, Montana, 59101
St. Vincent Frontier Cancer Center
Billings, Montana, 59102
The University of Vermont Medical Center
Burlington, Vermont, 05401
Charleston Cancer Center
Charleston, South Carolina, 29406
Northwestern University
Chicago, Illinois, 60611
Ellis Fichel Cancer Center, University of Missouri
Columbia, Missouri, 65212
Ohio State University, James Cancer Center
Columbus, Ohio, 43210
St. Luke's University Health Network
Easton, Pennsylvania, 18045
Providence Regional Medical Center
Everett, Washington, 98201
UConn Health School of Dental Medicine
Farmington, Connecticut, 06030
Hunterdon Hematology Oncology, LLC Hunterdon Regional Cancer Center
Flemington, New Jersey, 08822
University of Indianan, Goshen Center for Cancer Care
Goshen, Indiana, 46526
St. Mary's Regional Cancer Center
Grand Junction, Colorado, 81501
East Carolina University, Leo W. Jenkins Cancer Center
Greenville, North Carolina, 27834
Pasco Pinellas Cancer Center
Holiday, Florida, 34691
Department of Radiation Oncology University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Henry Ford Allegiance Health
Jackson, Michigan, 49201
Mountain States Health Alliance
Johnson City, Tennessee, 36704
Fowler Family Center for Cancer Care
Jonesboro, Arkansas, 72401
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Lakeland Regional Health Cancer Center
Lakeland, Florida, 32504
University of Kentucky, Albert B. Chandler Medical Center
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences- Winthrop P. Rockefeller Cancer Institute
Little Rock, Arkansas, 72205
VA Long Beach Healthcare System
Long Beach, California, 90822
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Louisville Hospital, James Graham Brown Cancer Center
Louisville, Kentucky, 40202
Clinical Trials and Research Associates, Inc.
Montebello, California, 90604
West Virginia University
Morgantown, West Virginia, 26506
Jersey Shore University Medical Center- Hackensack Meridian Health
Neptune City, New Jersey, 07753
Tulane Cancer Center
New Orleans, Louisiana, 70112
UC Irvine Chao Family Comprehensive Cancer Center
Orange, California, 92868
UF Health Cancer Center at Orlando Health
Orlando, Florida, 32806
Sacred Heart Medical Oncology Group
Pensacola, Florida, 32504
Thomas-Jefferson University Hospital-Bodine Center for Cancer Treatment
Philadelphia, Pennsylvania, 19107
University of Arizona Cancer Center at Dignity Health St. Joseph's
Phoenix, Arizona, 85004
Allegheny General Hospital, Allegheny Cancer Center
Pittsburgh, Pennsylvania, 15212
Texas Oncology
Plano, Texas, 75093
Lake Huron Medical Center
Port Huron, Michigan, 48060
Oregon Health and Science University
Portland, Oregon, 97239
VA Portland Health Care System
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Renown Cancer Institute
Reno, Nevada, 89502
VA Puget Sound Health Care System
Seattle, Washington, 98108
CHRISTUS Schumpert Cancer Treatment Center
Shreveport, Louisiana, 71101
Spartanburg Medical Center
Spartanburg, South Carolina, 29303
Cancer Care Northwest
Spokane, Washington, 99216
Baystate Regional Cancer Program
Springfield, Massachusetts, 01199
Stanford Cancer Institute
Stanford, California, 94305
Scott and White Memorial Hospital and Clinic
Temple, Texas, 76508
Montefiore Medical Center
The Bronx, New York, 10467
Toledo Clinic Cancer Center
Toledo, Ohio, 43623
University of Arizona
Tucson, Arizona, 85724
Hope Cancer Center
Tyler, Texas, 75701
Marion L. Shepard Cancer Center
Washington, North Carolina, 27889
Prairie Lakes Health Care System
Watertown, South Dakota, 57201
Wake Forest Health
Winston-Salem, North Carolina, 27157
Canada3 sites
Northeast Cancer Centre, Health Sciences North
Greater Sudbury, Ontario, P3E 5J1
Jewish General Hospital
Montreal, Quebec
Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-centre-du-Québec
Trois-Rivières, Quebec, G8Z 3R9
About this study
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
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.
Read the 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.
- Conditions
- Radiation Induced Oral Mucositis
- Being tested
- Low Dose GC4419: 30mg/day, High Dose GC4419: 90mg/day, Placebo, Intensity-Modulated Radiation Therapy, Cisplatin
- Keywords
- squamous cell carcinoma of the head and neck, oral cavity, oropharynx, intensity-modulated radiation therapy, chemotherapy, oral mucositis, superoxide dismutase, radioprotection
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Stomatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose GC4419: 30mg/dayDrug
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).
High Dose GC4419: 90mg/dayDrug
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).
PlaceboDrug
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 TherapyRadiation
Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks
CisplatinDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Low Dose GC4419: 30mg/day | Experimental | 30 mg GC4419/day prior to IMRT Receives: 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 Receives: Drug: High Dose GC4419: 90mg/day; Radiation: Intensity-Modulated Radiation Therapy; Drug: Cisplatin |
| Placebo | Placebo comparator | Placebo daily, prior to IMRT Receives: Drug: Placebo; Radiation: Intensity-Modulated Radiation Therapy; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Number of participants with treatment emergent adverse events (TEAE) per arm
Measured: First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks.
Number of Participants Who Experience Severe OM
Number of participants who experience severe OM from the first IMRT fraction through the last IMRT fraction
Measured: 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
Number of Participants who experienced Grade 4 OM
Measured: 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: number of IMRT fractions delivered at onset of severe OM
Measured: 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
Number of Participants who experienced Grade 4 OM
Measured: Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks.
Number of Participants With Tumor Outcomes Defined as Locoregional Failure, Distant Metastases, Disease Progression and Deaths
Effect of treatment assignment on tumor outcomes (locoregional failure, distant metastases, progression-free survival, overall survival) Only 73 subjects in Placebo Arm were analyzed for locoregional failure, distant disease and progression-free survival because 1 subject was determined after enrollment to have a non-head and neck cancer and was therefore excluded from these analyses
Measured: Up to 1 year following completion of chemoradiation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2015 (estimated)
- Study start12 Oct 2015
- Primary completion18 Sep 2017
- Study completion29 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Radiation Induced Oral MucositisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 223 participants (actual)
Sponsor and investigators
- Lead sponsor
- Galera Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jon T Holmlund, MD, Study chair, Chief Medical Officer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02508389
- Sponsor's protocol ID
- GT-201
- Status last verified
- Aug 2021
- First submitted
- 16 Jul 2015
- Last updated
- 20 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 36640725Anderson 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.
PubMed 35724774
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02508389
- Acronym / sponsor ID
- GT-201
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 223 participants (actual)
- Lead sponsor
- Galera Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Oct 2015
- Primary completion
- 18 Sep 2017 (actual)
- Study completion
- 29 Aug 2019 (actual)
- First posted
- 24 Jul 2015 (estimated)
- Results
- Posted 20 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose GC4419: 30mg/day | Experimental | Drug: Low Dose GC4419: 30mg/day, Radiation: Intensity-Modulated Radiation Therapy, Drug: Cisplatin30 mg GC4419/day prior to IMRT |
| High Dose GC4419: 90mg/day | Experimental | Drug: High Dose GC4419: 90mg/day, Radiation: Intensity-Modulated Radiation Therapy, Drug: Cisplatin90 mg GC4419/day prior to IMRT |
| Placebo | Placebo comparator | Drug: Placebo, Radiation: Intensity-Modulated Radiation Therapy, Drug: CisplatinPlacebo daily, prior to IMRT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Dose GC4419: 30mg/dayLow 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). | Drug | Low Dose GC4419: 30mg/day |
| High Dose GC4419: 90mg/dayHigh 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). | Drug | High Dose GC4419: 90mg/day |
| PlaceboPlacebo 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). | Drug | Placebo |
| Intensity-Modulated Radiation TherapyDaily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks | Radiation | High Dose GC4419: 90mg/day, Low Dose GC4419: 30mg/day, Placebo |
| CisplatinAdministered 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 | Drug | High Dose GC4419: 90mg/day, Low Dose GC4419: 30mg/day, Placebo |
Primary outcome
Duration (in Days) of Radiation Induced Severe Oral Mucositis (OM) Per World Health Organization (WHO) Criteria
Time frame: From start of Intensity-modulated radiation therapy (IMRT) through 8 weeks follow-up, an average of 15 weeks
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
6 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events
Time frame: First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks.
Number of Participants Who Experience Severe OM
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks.
Number of Participants With Tumor Outcomes Defined as Locoregional Failure, Distant Metastases, Disease Progression and Deaths
Time frame: Up to 1 year following completion of chemoradiation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36640725Mapuskar 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.
- Derived from this study: PubMed 35724774Anderson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jon T Holmlund, MD study chair
Chief Medical Officer
64 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose GC4419: 30mg/day, High Dose GC4419: 90mg/day and Intensity-Modulated Radiation Therapy in people with Radiation Induced Oral Mucositis, run by Galera Therapeutics, Inc. at 64 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 64 sites in United States, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration (in Days) of Radiation Induced Severe Oral Mucositis (OM) Per World Health Organization (WHO) Criteria (time frame: From start of Intensity-modulated radiation therapy (IMRT) through 8 weeks follow-up, an average of 15 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02508389, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2021.