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

Radiation Induced Oral Mucositis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02508389
• Other study ID #: GT-201
• Status: Completed
• Phase: Phase 2
• Start date: October 12, 2015
• Est. completion date: August 29, 2019

Study information

• Verified date: August 2021
• Source: Galera Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 carcinoma of the head and neck.

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 information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: August 29, 2019
• Est. primary completion date: September 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mucositis
• Radiation Induced Oral Mucositis
• Stomatitis

Intervention

Drug:
• 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).
• 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).
• 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).

Radiation:
• Intensity-Modulated Radiation Therapy
Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks

Drug:
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Galera Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Treatment-Emergent Adverse Events	Number of participants with treatment emergent adverse events (TEAE) per arm	First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks.
Secondary	Number of Participants Who Experience Severe OM	Number of participants who experience severe OM from the first IMRT fraction through the last IMRT fraction	Minimum of 60 Gy administered to tumor, approximately 30 IMRT fractions, which is estimated to be 6-7 weeks.
Secondary	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	First dose of IMRT through the completion of IMRT, estimated to be up to 6-7 weeks.
Secondary	Number of IMRT Fractions Delivered at Onset of Severe OM	Onset of severe 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.
Secondary	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	Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks.
Secondary	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	Up to 1 year following completion of chemoradiation.