Head and Neck Cancer, Oral Mucositis
Conditions
Brief summary
GTI-4419-202 is a Phase 2 open-label study of the effects of GC4419 (IV) when administered in combination with IMRT and cisplatin to up to subjects with head and neck cancer, who are at high risk for Severe Oral Mucositis (SOM)
Detailed description
Subjects will receive 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 100 mg/m2 once every three weeks for 3 doses or 40 mg/m2 once weekly for 6-7 doses (Investigator's choice). All subjects will be assessed twice weekly for Oral Mucositis (OM) per WHO grading criteria until 28 days post end of study treatment period (last day of IMRT).
Interventions
DRUGDrug: GC4419
GC4419 60 Minute Infusion
RADIATIONIntensity-modulated radiation therapy (IMRT)
2.0 to 2.2 Gy daily over 7 weeks
DRUGCisplatin
100mg/m2 once every 3 weeks or 40mg/m2 once weekly for 6-7 doses
Sponsors
Galera Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
To evaluate the effects of GC4419 in subjects with head and neck cancer, who are at high risk for Severe Oral Mucositis (SOM)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologically-confirmed diagnosis of locally advanced squamous cell carcinoma of the head and neck that will be treated with cisplatin plus concurrent IMRT. 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 of 60-72 Gy. 3. Patients who have had prior surgery may be eligible, 4. Treatment plan to receive standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) or weekly (40 mg/m2 for 6-7 doses). 5. Age 18 years or older 6. ECOG performance status ≤ 2 7. Adequate hematologic function 8. Adequate renal and liver function Alkaline phosphatase ≤ 2.5 ULN
Exclusion criteria
1. Metastatic disease 2. Prior radiotherapy to the region of the study cancer or adjacent anatomical sites 3. Prior induction chemotherapy or plans for chemotherapy to be administered only sequentially with IMRT 4. Planned concurrent chemotherapy other than single agent cisplatin 5. Receiving any approved or investigational anti-cancer agent 6. Concurrent participation in another interventional clinical study 7. Inability to eat soft solid food at baseline for reasons other than mouth soreness after surgery or dental procedures 8. Complete reliance on parenteral or gastrointestinal tube-delivered nutrition at baseline 9. Malignant tumors other than head and neck cancer (HNC) within the last 5 years 10. Active infectious disease excluding oral candidiasis 11. Presence of oral mucositis at baseline. 12. Known history of human immunodeficiency virus (HIV) or active hepatitis B/C 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent AE's | First dose of study medication through the 30 days following the last dose of IMRT, GC4419, or cisplatin (whichever occurs last) which is estimated to be 11 weeks | Number of Subjects with at Least One Treatment Emergent Adverse Event (TEAE) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Severe OM | From start of Intensity-modulated radiation therapy (IMRT) through approximately 30 fractions which is estimated to be 6-7 weeks. | Cumulative Incidence of WHO Grade 3-4 from the start of IMRT through the end of the study treatment period (last day of IMRT) |
Countries
Belgium, Czechia, Germany, Poland, Spain, Switzerland
Participant flow
Recruitment details
A total of 38 subjects were enrolled to the study (signed an ICF). Only 37 of these subjects were dosed on the trial and part of the ITT population (enrolled subjects who received 1 dose of study medication). The 1 subject that was enrolled but was not dosed withdrew their consent prior to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Active Arm 90mg GC4419 by IV
Drug: GC4419: GC4419 60 Minute Infusion | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Open Label Active Arm |
|---|---|
| Age, Customized Age Group, years <18 | 0 Participants |
| Age, Customized Age Group, years 18-65 | 25 Participants |
| Age, Customized Age Group, years 66-75 | 10 Participants |
| Age, Customized Age Group, years >75 | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Region of Enrollment Belgium | 8 participants |
| Region of Enrollment Czechia | 4 participants |
| Region of Enrollment Germany | 1 participants |
| Region of Enrollment Poland | 8 participants |
| Region of Enrollment Spain | 9 participants |
| Region of Enrollment Switzerland | 7 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 37 |
| other Total, other adverse events | 36 / 37 |
| serious Total, serious adverse events | 18 / 37 |
Outcome results
Primary
Incidence of Treatment Emergent AE's
Number of Subjects with at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: First dose of study medication through the 30 days following the last dose of IMRT, GC4419, or cisplatin (whichever occurs last) which is estimated to be 11 weeks
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE Leading to Discontinuation of GC4419 | 1 Participants |
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE | 36 Participants |
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE Related to GC4419 | 12 Participants |
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE Related to IMRT | 33 Participants |
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE Related to Chemotherapy | 35 Participants |
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE Leading to Discontinuation | 11 Participants |
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE Leading to Discontinuation of IMRT | 1 Participants |
| Open Label Active Arm | Incidence of Treatment Emergent AE's | TEAE Leading to Discontinuation of Chemotherapy | 10 Participants |
Secondary
Cumulative Incidence of Severe OM
Cumulative Incidence of WHO Grade 3-4 from the start of IMRT through the end of the study treatment period (last day of IMRT)
Time frame: From start of Intensity-modulated radiation therapy (IMRT) through approximately 30 fractions which is estimated to be 6-7 weeks.
Population: Per Protocol Population defined as subjects who received at least 60 Gy of IMRT and at least 25 doses of GC4419.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Active Arm | Cumulative Incidence of Severe OM | 54.5 percentage of Subjects with SOM |