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

Phase 2

Completed

Conditions: Radiation Induced Oral Mucositis

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

Registration Number: NCT02508389

Lead Sponsor: Galera Therapeutics, Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 223

Inclusion Criteria

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:
- 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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Dose GC4419: 30mg/day	Intensity-Modulated Radiation Therapy	30 mg GC4419/day prior to IMRT
High Dose GC4419: 90mg/day	Intensity-Modulated Radiation Therapy	90 mg GC4419/day prior to IMRT
Placebo	Placebo	Placebo daily, prior to IMRT
Placebo	Intensity-Modulated Radiation Therapy	Placebo daily, prior to IMRT
Low Dose GC4419: 30mg/day	Cisplatin	30 mg GC4419/day prior to IMRT
High Dose GC4419: 90mg/day	Cisplatin	90 mg GC4419/day prior to IMRT
Placebo	Cisplatin	Placebo daily, prior to IMRT

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 with treatment emergent adverse events (TEAE) per arm
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 experience severe OM from the first IMRT fraction through the last IMRT fraction
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 Participants who experienced Grade 4 OM
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.	Onset of severe OM: number of IMRT fractions delivered at onset of severe OM
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.	Number of Participants who experienced Grade 4 OM
Number of Participants With Tumor Outcomes Defined as Locoregional Failure, Distant Metastases, Disease Progression and Deaths	Up to 1 year following completion of chemoradiation.	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

Trial Locations

Locations (64): USC Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Ohio State University, James Cancer Center
🇺🇸
Columbus, Ohio, United States
Thomas-Jefferson University Hospital-Bodine Center for Cancer Treatment
🇺🇸
Philadelphia, Pennsylvania, United States
Allegheny General Hospital, Allegheny Cancer Center
🇺🇸
Pittsburgh, Pennsylvania, United States
University of Kentucky, Albert B. Chandler Medical Center
🇺🇸
Lexington, Kentucky, United States
St. Mary's Regional Cancer Center
🇺🇸
Grand Junction, Colorado, United States
Ashland-Bellefonte Cancer Center
🇺🇸
Ashland, Kentucky, United States
Jersey Shore University Medical Center- Hackensack Meridian Health
🇺🇸
Neptune, New Jersey, United States
Stanford Cancer Institute
🇺🇸
Stanford, California, United States
Lakeland Regional Health Cancer Center
🇺🇸
Lakeland, Florida, United States
UC Irvine Chao Family Comprehensive Cancer Center
🇺🇸
Orange, California, United States
Pasco Pinellas Cancer Center
🇺🇸
Holiday, Florida, United States
CHRISTUS Schumpert Cancer Treatment Center
🇺🇸
Shreveport, Louisiana, United States
Billings Clinic
🇺🇸
Billings, Montana, United States
Hunterdon Hematology Oncology, LLC Hunterdon Regional Cancer Center
🇺🇸
Flemington, New Jersey, United States
East Carolina University, Leo W. Jenkins Cancer Center
🇺🇸
Greenville, North Carolina, United States
VA Puget Sound Health Care System
🇺🇸
Seattle, Washington, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States
St. Vincent Frontier Cancer Center
🇺🇸
Billings, Montana, United States
VA Long Beach Healthcare System
🇺🇸
Long Beach, California, United States
University of Arizona
🇺🇸
Tucson, Arizona, United States
University of Arkansas for Medical Sciences- Winthrop P. Rockefeller Cancer Institute
🇺🇸
Little Rock, Arkansas, United States
Fowler Family Center for Cancer Care
🇺🇸
Jonesboro, Arkansas, United States
Clinical Trials and Research Associates, Inc.
🇺🇸
Montebello, California, United States
UConn Health School of Dental Medicine
🇺🇸
Farmington, Connecticut, United States
Sacred Heart Medical Oncology Group
🇺🇸
Pensacola, Florida, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Indianan, Goshen Center for Cancer Care
🇺🇸
Goshen, Indiana, United States
Ellis Fichel Cancer Center, University of Missouri
🇺🇸
Columbia, Missouri, United States
AnMed Health Cancer Center
🇺🇸
Anderson, South Carolina, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Mountain States Health Alliance
🇺🇸
Johnson City, Tennessee, United States
University of Tennessee Medical Center
🇺🇸
Knoxville, Tennessee, United States
The University of Vermont Medical Center
🇺🇸
Burlington, Vermont, United States
Scott and White Memorial Hospital and Clinic
🇺🇸
Temple, Texas, United States
Hope Cancer Center
🇺🇸
Tyler, Texas, United States
Cancer Care Northwest
🇺🇸
Spokane, Washington, United States
Providence Regional Medical Center
🇺🇸
Everett, Washington, United States
West Virginia University
🇺🇸
Morgantown, West Virginia, United States
Northeast Cancer Centre, Health Sciences North
🇨🇦
Sudbury, Ontario, Canada
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Fundación de Investigación
🇵🇷
San Juan, Puerto Rico
Henry Ford Allegiance Health
🇺🇸
Jackson, Michigan, United States
Department of Radiation Oncology University of Iowa Hospitals & Clinics
🇺🇸
Iowa City, Iowa, United States
Marion L. Shepard Cancer Center
🇺🇸
Washington, North Carolina, United States
Baystate Regional Cancer Program
🇺🇸
Springfield, Massachusetts, United States
Lake Huron Medical Center
🇺🇸
Port Huron, Michigan, United States
Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-centre-du-Québec
🇨🇦
Trois-Rivières, Quebec, Canada
Renown Cancer Institute
🇺🇸
Reno, Nevada, United States
Toledo Clinic Cancer Center
🇺🇸
Toledo, Ohio, United States
Texas Oncology
🇺🇸
Plano, Texas, United States
St. Luke's University Health Network
🇺🇸
Easton, Pennsylvania, United States
Prairie Lakes Health Care System
🇺🇸
Watertown, South Dakota, United States
University of Arizona Cancer Center at Dignity Health St. Joseph's
🇺🇸
Phoenix, Arizona, United States
University of Louisville Hospital, James Graham Brown Cancer Center
🇺🇸
Louisville, Kentucky, United States
Tulane Cancer Center
🇺🇸
New Orleans, Louisiana, United States
VA Portland Health Care System
🇺🇸
Portland, Oregon, United States
UF Health Cancer Center at Orlando Health
🇺🇸
Orlando, Florida, United States
Charleston Cancer Center
🇺🇸
Charleston, South Carolina, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest Health
🇺🇸
Winston-Salem, North Carolina, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States