Effects of Intravenous GC4419 on the Incidence and Severity of Esophagitis Due to Chemoradiotherapy for Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2a Open-Label Trial of the Effects of Intravenous GC4419 on the Incidence and Severity of Esophagitis in Subjects Receiving Chemoradiotherapy for Lung Cancer

Conditions
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Esophagitis

Intervention / Treatment
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* Drug: GC4419 (avasopasem manganese)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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% Age 18 years or older ECOG performance status ≤ 2 Adequate hematologic, renal and liver function Use of highly effective contraception Exclusion Criteria: Metastatic disease Prior radiation therapy to the region of the study cancer Subjects not receiving chemotherapy Grade 2 or greater esophagitis at baseline Inability to provide information in the electronic symptom-reporting device Receiving any approved or investigational immunotherapy, targeted therapy, hormone therapy, or biologic therapy Participation in another clinical trial or use of another investigational agent within 30 days of first does of GC4419 Malignant tumors other than the current lung cancer within the last 5 years Previous diagnosis of pneumonitis Untreated, active infectious disease requiring systemic anti-infective therapy Untreated HIV or active hepatitis B/C Females who are pregnant or breastfeeding Known allergies or intolerance to chemotherapy 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 Clinically significant heart disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GC4419 (avasopasem manganese)<br> | Drug: GC4419 (avasopasem manganese)<br>* 90 mg, by 60-minute IV infusion, prior to each fraction of RT<br>* Other names: Avasopasem manganese;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From the first radiation therapy fraction through the end of the study treatment period, which is estimated to be 6 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From the first radiation therapy fraction through 4 weeks after the completion of chemoradiotherapy, which is estimated to be 10 weeks | 
| 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. | From the first radiation therapy fraction through the completion of chemoradiotherapy, which is estimated to be 6 weeks. |