4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN): A Phase II Clinica

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DESCRIPTION (provided by applicant): The principal goal of this research project will be to evaluate 4-demethyl-4- cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), a polychlorinated cholesterol carbonate as anticancer therapy for patients with advanced cancer in a Phase II clinical trial. During pre-clinical studies DM-CHOC-PEN produced complete remissions with long term survival vs. intracranially (IC) implanted human gliomas and breast cancer xenograft and melanoma murine models in mice. In the recently completed Phase I clinical trial (that included patients with CNS involvement), the drug proved to be non-neurotoxic. Several patients - sarcoma, GBM, breast cancer (CNS lesions) have demonstrated PFS > 6-18 mos. and one (sarcoma spread to the sine) has NED x 12+ mos. Renal, pulmonary and hematological side effects were not observed; dose limiting effect was hepatic - elevated bilirubin. Complete pharmacokinetic studies/parameters are reviewed. The clinical product is an emulsion with stability under refrigeration - 1.5 yrs. The package has been reviewed by IRBs and FDA - IND 68,876. The aims will include: 1) Initiate a Phase II trial with DM-CHOC-PEN administered IV to patients with advanced or recurrent cancer (+/- CNS involvement acceptable) and verify that the proposed dose is acceptable, monitor pharmacodynamics and toxicities. 2) Monitor tumor responses to DM-CHOC-PEN per imaging/examinations using RECIST guidelines. 3) Electronically store/analyze clinical data for toxicity, responses and tumor-organ relationships. 4) Continue to bank tumor tissue from pre- and post-treated patients when possible and assay tumor - drug/metabolite content and bio-markers; store blood samples for future studies, i.e. Caris Target Now, etc. 5) Prepare a FDA presentation for subsequent Phase II (binary drug) or III (single drug) trials with DM-CHOC-PEN in patients with specific tumor types.