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

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

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.

Inclusion Criteria:

1. 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.
2. Histologically proven oral cavity or oropharyngeal moderate or severe dysplasia/CIS as diagnosed by standard pathological methods and a visible lesion on oral exam.
3. Measurable disease - minimum lesion size of 8 x 3 mm before initial biopsy
4. Willing to provide blood, oral rinse and tissue from diagnostic biopsies
5. Leukocytes >=3,000/microliter
6. Absolute neutrophil count >= 1,000/microliter, Platelets >= 100,000/microliter, Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), 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). Exceptions to this Inclusion Criteria can be made if labs are deemed not clinically significant by the principal investigator (PI).
7. 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.
8. Able to take oral medication.
9. Able to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Pregnant women.
2. Subjects who have had surgery of the oral cavity, teeth, or gums within the previous 8 weeks excluding biopsies and tooth extractions.
3. Subjects who have had a fracture of the mandible or maxilla within the previous 8 weeks.
4. Inability to complete enrollment forms due to any mental status or language problems (e.g. dementia, head injury, overall illness).
5. History of prior head and neck squamous cell carcinomas (HNSCC) unless curatively treated 1 year or more prior.
6. 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.
7. Subjects with other related diseases or the oral cavity or oropharynx, as determined to be significant by the PI.
8. History of allergic reactions attributed to compounds of similar chemical composition to Curcumin (turmeric).
9. Active or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension. Exceptions to this Exclusion Criteria can be made if patient status is deemed not clinically significant by the PI.
10. Severe thrombocytopenia increasing the risk of biopsy.
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.