A Phase 2 clinical trial of topical uracil for the prevention of capecitabine induced hand-foot syndrome

Problem to be SolvedCapecitabine is a widely prescribed and orally available prodrug of the chemotherapeutic agentfluorouracilFUThe principle dose schedule limiting toxicity associated with its use is Hand Foot syndromeHFSand occurs inof patients receiving capecitabineHFS manifests in the hands and feet of patientsand rapidly progresses to painful peelingblisteringand bleeding that commonly require narcoticsThere is no approved treatment to prevent or treat HFSand management typically involves disruptions in capecitabine dosing regimenswhich can diminish the efficacy of the drug in its approved indicationsThere remains a significant need to develop a treatment for HFS that would permit uninterrupted capecitabine therapy at optimal dosing regimens and improve quality of life for patientsProduct and Long Term GoalNanometicsd b a PHD BiosciencesPHDis developing anuracil topical creamUTCto prevent HFSwhich has successfully completed a Phaseclinical trial inpatientsTechnical InnovationUracil is an endogenous metabolite and competitive substrate to enzymes that catabolize capecitabine to the toxic metabolites responsible for HFSWhen administered topically to the hands and feet of patients as UTCuracil is absorbed by diffusion and inhibits local cutaneous toxicity without impacting the systemic anti cancer activity ofFUPhase I SBIR Equivalent OutcomesIn a randomizeddouble blind placebo controlled Phaseclinical study in metastatic breast cancer patients receiving capecitabinethe risk of andgtGradeHFSa severity that is associated with pain and impairment of daily activitieswas lower in the UTC treated groupthan the placebo groupThe UTC group also had a tripling of time to andgtGradeHFS relative to placebotreatment group hazard ratiopand an excellent safety profile with no adverse eventsDirect Phase II ObjectivesDemonstrate the safety and efficacy of UTC inmetastatic breast cancer patientsmBCbeing treated with capecitabineExpected OutcomesConcurrent treatment with UTC among women with mBC treated with capecitabine will delay a meaningfully detrimental increase in patient reported pain associated with the development of HFSCommercial ApplicationUTC will be commercialized as a topical treatment for capecitabine patients Hand foot syndromeHFSis the principle dose limiting toxicity of the widely prescribed chemotherapeutic capecitabine and occurs inof capecitabine usersCurrently there is no treatment for HFSwhich can be a debilitating condition that forces physicians to disrupt dosing regimenspotentially diminishing the efficacy of capecitabine in its approved indicationsThis project seeks to complete a phaseclinical trial of auracil topical cream to prevent HFS in metastatic breast cancer patients being treated with capecitabine