Esophagitis
Conditions
Brief summary
GTI-4419-203 will be an open-label, multi-center study to evaluate GC4419 (avasopasem manganese) administered intravenous (IV) for the reduction of radiation induced esophagitis in subjects receiving chemoradiotherapy for unresectable Stage 3A/3B or post-operative Stage 2B Non-Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC) treatable with chemoradiotherapy.
Interventions
DRUGGC4419 (avasopasem manganese)
90 mg, by 60-minute IV infusion, prior to each fraction of RT
Sponsors
Galera Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects scheduled to be treated with (definitive or adjuvant) radiation therapy in combination with chemotherapy once daily for Stage 3A/3B or post-operative Stage 2B NSCLC or limited stage SCLC 2. Treatment plan for subjects show that 5 cm of the esophagus for at least one surface, is included in the 60 Gy isodose volume. Dose volume histograms show esophagus dose exposure meet V38\>30% and/or V60\>20% 3. Age 18 years or older 4. ECOG performance status ≤ 2 5. Adequate hematologic, renal and liver function 6. Use of highly effective contraception
Exclusion criteria
1. Metastatic disease 2. Prior radiation therapy to the region of the study cancer 3. Subjects not receiving chemotherapy 4. Grade 2 or greater esophagitis at baseline 5. Inability to provide information in the electronic symptom-reporting device 6. Receiving any approved or investigational immunotherapy, targeted therapy, hormone therapy, or biologic therapy 7. Participation in another clinical trial or use of another investigational agent within 30 days of first does of GC4419 8. Malignant tumors other than the current lung cancer within the last 5 years 9. Previous diagnosis of pneumonitis 10. Untreated, active infectious disease requiring systemic anti-infective therapy 11. Untreated HIV or active hepatitis B/C 12. Females who are pregnant or breastfeeding 13. Known allergies or intolerance to chemotherapy and similar platinum-containing compounds 14. Requirement for concurrent treatment with nitrates or other drugs that may create a risk for a precipitous decrease in blood pressure 15. Clinically significant heart disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. | From the first radiation therapy fraction through the end of the study treatment period, which is estimated to be 6 weeks. | Those subjects in the primary efficacy population that experience acute radiation esophagitis (Grade \>/=2; NCI CTCAE version 5) through the end of chemoradiotherapy for NSCLC or SCLC when treated with avasopasem. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization Grade 4: life-threatening consequences; urgent operative intervention indicated Grade 5: death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy | From the first radiation therapy fraction through 4 weeks after the completion of chemoradiotherapy, which is estimated to be 10 weeks | Those subjects in the in the primary efficacy population that experience Grade \>/= 2 (NCI CTCAE version 5) acute radiation esophagitis through 4 weeks after completion of chemoradiotherapy for NSCLC or SCLC when treated with avasopasem. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization Grade 4: life-threatening consequences; urgent operative intervention indicated Grade 5: death |
| Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | From the first radiation therapy fraction through the completion of chemoradiotherapy, which is estimated to be 6 weeks. | Those subjects in the per protocol population that experienced Grade 3-4 acute radiation esophagitis through the completion of chemoradiotherapy. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated; Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated; Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization; Grade 4: life-threatening consequences; urgent operative intervention indicated; Grade 5: Death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GC4419 GC4419: 90 mg, by 60-minute IV infusion, prior to each fraction of RT | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 11 |
| Overall Study | Other | 1 |
| Overall Study | Study Terminated Early By Sponsor | 7 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | GC4419 |
|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 9.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 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 United States | 39 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 22 Participants |
| Type of Lung Cancer NSCLC | 32 participants |
| Type of Lung Cancer SCLC | 7 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 39 |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 15 / 39 |
Outcome results
Primary
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added.
Those subjects in the primary efficacy population that experience acute radiation esophagitis (Grade \>/=2; NCI CTCAE version 5) through the end of chemoradiotherapy for NSCLC or SCLC when treated with avasopasem. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization Grade 4: life-threatening consequences; urgent operative intervention indicated Grade 5: death
Time frame: From the first radiation therapy fraction through the end of the study treatment period, which is estimated to be 6 weeks.
Population: Primary Efficacy Population included all subjects who received at lease 1 dose of GC4419 (avasopasem manganese) and either completed their radiation therapy or discontinued their radiation therapy early but were known to have had acute radiation esophagitis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. | Condition Not Present | 7 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. | Grade 1 | 6 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. | Grade 2 | 17 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. | Grade 3 | 2 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. | Grade 4 | 0 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. | Grade 5 | 0 Participants |
Secondary
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy.
Those subjects in the per protocol population that experienced Grade 3-4 acute radiation esophagitis through the completion of chemoradiotherapy. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated; Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated; Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization; Grade 4: life-threatening consequences; urgent operative intervention indicated; Grade 5: Death.
Time frame: From the first radiation therapy fraction through the completion of chemoradiotherapy, which is estimated to be 6 weeks.
Population: Per protocol population defined as those subjects completing chemoradiation therapy and at least 5 weeks of GC4419
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GC4419 (Avasopasem Manganese) | Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | Condition Not Present | 7 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | Grade 1 | 6 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | Grade 2 | 13 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | Grade 3 | 1 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | Grade 4 | 0 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | Grade 5 | 0 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. | Assessment Not Performed | 2 Participants |
Secondary
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy
Those subjects in the in the primary efficacy population that experience Grade \>/= 2 (NCI CTCAE version 5) acute radiation esophagitis through 4 weeks after completion of chemoradiotherapy for NSCLC or SCLC when treated with avasopasem. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization Grade 4: life-threatening consequences; urgent operative intervention indicated Grade 5: death
Time frame: From the first radiation therapy fraction through 4 weeks after the completion of chemoradiotherapy, which is estimated to be 10 weeks
Population: Primary Efficacy Population included all subjects who received at lease 1 dose of GC4419 (avasopasem manganese) and either completed their radiation therapy or discontinued their radiation therapy early but were known to have had acute radiation esophagitis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy | Condition Not Present | 19 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy | Grade 1 | 4 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy | Grade 2 | 10 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy | Grade 3 | 1 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy | Grade 4 | 0 Participants |
| GC4419 (Avasopasem Manganese) | Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy | Grade 5 | 0 Participants |