A Proof of Concept Trial Investigating Safety and Efficacy of APG-157 in Oral Dysplasia

Study Overview
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Brief Summary
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The purpose of this study is to assess whether APG-157 can reduce the tumor size in participants with the study disease. Another purpose is to find out about the effects of APG-157 on certain tumor markers and oral rinses in participants with the study disease.

Official Title
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Phase II A Proof of Concept Trial Investigating Safety and Efficacy of APG-157 in Oral Dysplasia

Conditions
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Oropharyngeal Dysplasia, Oral Cavity Dysplasia, Oral Carcinoma in Situ

Intervention / Treatment
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* Drug: APG-157


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients age > 18 years with biopsy-proven moderate to severe oral dysplasia or carcinoma in situ (CIS) and a visible lesion. Sites include all oral cavity as well as oropharyngeal dysplasia that is accessible in the outpatient clinic. Histologically proven oral cavity or oropharyngeal moderate or severe dysplasia/CIS as diagnosed by standard pathological methods and a visible lesion on oral exam. Measurable disease - minimum lesion size of 8 x 3 mm before initial biopsy Willing to provide blood, oral rinse and tissue from diagnostic biopsies Leukocytes >=3,000/microliter Absolute neutrophil count >= 1,000/microliter, Platelets >= 100,000/microliter, Total bilirubin =< 1.5 x institutional upper limit (IUL) of normal (UNL), aspartate aminotransferase (AST), serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT) and serum glutamic pyruvic transaminase (SGPT) =< 1.5 x institutional upper limit of normal (ULN). Willing to use adequate contraception, subject or partner has had a vasectomy or partner is using effective birth control or is post-menopausal for the duration of the study. Able to take oral medication. Able to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Pregnant women. Subjects who have had surgery of the oral cavity, teeth, or gums within the previous 8 weeks excluding biopsies and tooth extractions. Subjects who have had a fracture of the mandible or maxilla within the previous 8 weeks. Inability to complete enrollment forms due to any mental status or language problems (e.g. dementia, head injury, overall illness). History of prior head and neck squamous cell carcinomas (HNSCC) unless curatively treated 1 year or more prior. Use of chemotherapy and/or radiation for any malignancy (excluding nonmelanoma skin cancer and cancer confined to organs with removal as only treatment) in the past 2 years. Subjects with other related diseases or the oral cavity or oropharynx, as determined to be significant by the PI. History of allergic reactions attributed to compounds of similar chemical composition to Curcumin (turmeric). Active or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension. Severe thrombocytopenia increasing the risk of biopsy. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

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: APG-157 Therapy<br>Participants will receive APG-157 for up to 12 weeks. | Drug: APG-157<br>* Participants will take 200mg (2 x 100mg pastilles) of APG-157 therapy orally (PO) three times daily during each 4-week cycle for up to three cycles. Cycle three is optional.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Response Rate | The pathologic response rate among participants receiving study treatment will be assessed. The pathologic response rate is defined as the percentage of participants with mild or no dysplasia after receiving study therapy. Response will be assessed on the basis of clinical, radiologic, molecular and pathologic criteria consistent with Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria, per physician discretion. | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate | The clinical response rate among participants receiving study treatment will be assessed. The clinical response rate is defined as the percentage of participants with complete response (CR) and/or partial response (PR) after receiving study therapy. Response will be assessed on the basis of clinical, radiologic, molecular and pathologic criteria consistent with Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria. | Up to 12 weeks | 
| Change in Lesion Appearance Before and After Protocol Therapy | Change in lesion appearance will be assessed using criteria consistent with Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria, found at time of oral exam per physician discretion. | Baseline, 12 weeks post-intervention, Up to 28 months | 
| Number of Treatment-Related Adverse Events and Serious Adverse Events | The number of treatment-related adverse events (AEs) and serious adverse events (SAEs) in participants receiving protocol therapy will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion. | Up to 16 weeks |