Ph 2 Open Label Study of GC4419 to Reduce SOM Associated With Chemoradiotherapy for Head and Neck Cancer

Study Overview
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Brief Summary
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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
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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).

Official Title
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An Open Label Multi-Center Study of the Effects of GC4419 When Administered to Reduce the Incidence and Severity of Severe Oral Mucositis Associated With Chemo RT for Locally Advanced, Non-Metastatic Head and Neck Cancer

Conditions
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Head and Neck Cancer, Oral Mucositis

Intervention / Treatment
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* Drug: Drug: GC4419
* Radiation: Intensity-modulated radiation therapy (IMRT)
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically-confirmed diagnosis of locally advanced squamous cell carcinoma of the head and neck that will be treated with cisplatin plus concurrent IMRT. 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. Patients who have had prior surgery may be eligible, 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). Age 18 years or older ECOG performance status ≤ 2 Adequate hematologic function Adequate renal and liver function Alkaline phosphatase ≤ 2.5 ULN Exclusion Criteria: Metastatic disease Prior radiotherapy to the region of the study cancer or adjacent anatomical sites Prior induction chemotherapy or plans for chemotherapy to be administered only sequentially with IMRT Planned concurrent chemotherapy other than single agent cisplatin Receiving any approved or investigational anti-cancer agent Concurrent participation in another interventional clinical study Inability to eat soft solid food at baseline for reasons other than mouth soreness after surgery or dental procedures Complete reliance on parenteral or gastrointestinal tube-delivered nutrition at baseline Malignant tumors other than head and neck cancer (HNC) within the last 5 years Active infectious disease excluding oral candidiasis Presence of oral mucositis at baseline. Known history of human immunodeficiency virus (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, in the judgment of the treating Investigator, create a risk for a precipitous decrease in blood pressure.

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: Prevention
Intervention Model: Single Group Assignment
Interventional 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)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label Active Arm<br>90mg GC4419 by IV | Drug: Drug: GC4419<br>* GC4419 60 Minute Infusion<br>Radiation: Intensity-modulated radiation therapy (IMRT)<br>* 2.0 to 2.2 Gy daily over 7 weeks<br>Drug: Cisplatin<br>* 100mg/m2 once every 3 weeks or 40mg/m2 once weekly for 6-7 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent AE's | Number of Subjects with at Least One Treatment Emergent Adverse Event (TEAE) | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | From start of Intensity-modulated radiation therapy (IMRT) through approximately 30 fractions which is estimated to be 6-7 weeks. |