Oral Mucositis
Conditions
Keywords
Oral Mucositis, Superoxide Dismutase Mimetic, Cisplatin, Intensity-Modulated Radiation Therapy, Chemoradiation, OM, IMRT, Head and Neck Cancer, Squamous Cell Carcinoma, SCC, Oral Cavity, Oropharnyx, Mouth Sores, avasopasem mangenese
Brief summary
The purpose of the phase 3, clinical study is to determine if GC4419 (avasopasem manganese) administered prior to intensity-modulated radiation therapy (IMRT) reduces the 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.
Interventions
DRUGGC4419 90mg
60 minute IV infusion
DRUGPlacebo
60 minute IV infusion
Sponsors
Galera Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* squamous cell carcinoma of the head and neck * treatment plan to receive IMRT delivered as single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose of 60-72 Gy * Treatment plan to receive standard cisplatin monotherapy * Age 18 years or older * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Adequate hematologic, renal and liver function * Negative serum pregnancy test * Use of effective contraception
Exclusion criteria
* Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands * Metastatic disease * Prior radiotherapy to the region of the study cancer or adjacent anatomical * Prior induction chemotherapy * Receiving any approved or investigational anti-cancer agent other than those provided for in this study * Concurrent participation in another interventional clinical study * Inability to eat soft solid food at baseline * Malignant tumors other than HNC within the last 5 years * Active infectious disease excluding oral candidiasis * Presence of oral mucositis at baseline * Known history of HIV or active hepatitis B/C * 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 create a risk for a precipitous decrease in blood pressure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Severe Oral Mucositis | From the first IMRT fraction through the end of the study treatment period (completion of study drug administration, IMRT and chemotherapy), which is estimated to be 7 weeks. | Cumulative incidence of severe oral mucositis is defined as the proportion of subjects with any occurrence of WHO Grade 3 to 4 OM, during the Study Treatment Period. Incidence of severe OM is defined as any occurrence of WHO Grade 3 or 4 OM through the last IMRT fraction after the start of IMRT. Incidence was imputed using multiple imputation for subjects with incomplete follow-up for severe OM through 60 Gy who did not have an occurrence of severe OM before the last IMRT fraction. |
Countries
Canada, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GC4419 (Avasopasem Manganese) GC4419 (avasopasem manganese): 60 minute IV infusion | 241 |
| Placebo Placebo: 60 minute IV infusion | 166 |
| Total | 407 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 20 | 10 |
| Overall Study | Lost to Follow-up | 6 | 6 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Patient Non-Compliance | 0 | 1 |
| Overall Study | Patients Continuing in Long Term Follow Up | 88 | 71 |
| Overall Study | Randomized but not Treated | 13 | 7 |
| Overall Study | Subject Dosing Suspended due to Product Issue | 16 | 12 |
| Overall Study | Withdrawal by Subject | 20 | 4 |
Baseline characteristics
| Characteristic | GC4419 (Avasopasem Manganese) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 78 Participants | 55 Participants | 133 Participants |
| Age, Categorical Between 18 and 65 years | 163 Participants | 111 Participants | 274 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 1 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 222 Participants | 160 Participants | 382 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 5 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) White | 219 Participants | 158 Participants | 377 Participants |
| Region of Enrollment Canada | 33 participants | 24 participants | 57 participants |
| Region of Enrollment United States | 208 participants | 142 participants | 350 participants |
| Sex: Female, Male Female | 39 Participants | 17 Participants | 56 Participants |
| Sex: Female, Male Male | 202 Participants | 149 Participants | 351 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 241 | 10 / 166 |
| other Total, other adverse events | 240 / 241 | 166 / 166 |
| serious Total, serious adverse events | 81 / 241 | 52 / 166 |
Outcome results
Primary
Cumulative Incidence of Severe Oral Mucositis
Cumulative incidence of severe oral mucositis is defined as the proportion of subjects with any occurrence of WHO Grade 3 to 4 OM, during the Study Treatment Period. Incidence of severe OM is defined as any occurrence of WHO Grade 3 or 4 OM through the last IMRT fraction after the start of IMRT. Incidence was imputed using multiple imputation for subjects with incomplete follow-up for severe OM through 60 Gy who did not have an occurrence of severe OM before the last IMRT fraction.
Time frame: From the first IMRT fraction through the end of the study treatment period (completion of study drug administration, IMRT and chemotherapy), which is estimated to be 7 weeks.
Population: The Intent to treat population consisted of all randomized subjects who received at least 1 dose of avasopasem manganese or placebo (with the exception of subjects whose treatment course was discontinued due to the sponsor's voluntary suspension of dosing)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GC4419 (Avasopasem Manganese) 90mg | Cumulative Incidence of Severe Oral Mucositis | 53.8 percentage of patients |
| Placebo | Cumulative Incidence of Severe Oral Mucositis | 64.0 percentage of patients |