A-007: Immune Modulation of HPV - Associated Neoplasia

DESCRIPTION (provided by applicant): 4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) was originally developed as an immune modulator of immune deficiency associated cancerous growths. In a recent study, A-007 was administered as a topical gel to treat anogenital cancers associated with the human papillomavirus (HPV). There were no local or systemic toxicities and excellent responses were seen -76% CR. All patients with cervical or vaginal neoplasia either had complete elimination of HPV infections or the viral types reduced from high risk to low risk groups. Immunohistochemical (IHC) and computer modeling studies support animal data and the hypothesis that A-007 interacts with the protein tyrosine phosphatase (PTP) T-cell membrane receptor CD45 up-regulating T-cells and improving local immunity. The latter changes override the local neoplastic CIN transformations. Support is provided in the present application to evaluate A-007 as therapy for cervical intraepithelial neoplasia (CIN) associated with HPV. Literature indicates that up to 70% of the CIN I disease can spontaneously disappear. Thus, the present studies have been designed to randomize CIN I to a placebo vs. A-007. The placebo arm will allow for any immune stimulation that follows biopsies and local physical stimulation associated with manipulations of the cervix. The advanced stages of the disease - CIN II/Ill - will be treated only with A-007; since there are no other medical treatments for this stage of disease and surgery would be the next treatment of choice. The CIN I patients treated with placebos will be given the option to receive A-007 after one course, if disease remains. The specific objectives of this Phase II study will be to topically treat 250 with various stages of CIN infected with HPV and evaluate A-007's ability to reverse CIN changes and eliminate HPV. Local immune modulation will be closely monitored, and standard histopathology and viral assessments will be performed. The study will be performed at three qualified clinical centers.