Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy
Condition: Cancer of the Breast
MeSH terms: Breast Neoplasms
Intervention: Omeprazole
Intervention MeSH terms: Omeprazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      In preliminary laboratory science studies, the investigators show that proton pump inhibitors
      (PPIs) effectively inhibit human fatty acid synthase (FASN) and breast cancer cell survival.
      A preliminary retrospective study shows that PPI usage in breast cancer patients during
      chemotherapy significantly improved overall survival. The impact was most striking in
      patients with triple negative breast cancer (TNBC). Thus, PPIs may be repositioned as safe
      and effective breast cancer drugs to enhance the effect of chemotherapy.

      Many of the hurdles that slow progress from target, to lead compound, to investigational
      agent, to standard therapy are not barriers for the PPIs. The PPIs are FDA-approved,
      chronically used, and well tolerated so the investigators can move quickly from the
      laboratory to a proof of concept clinical trial. Incorporating the PPIs into standard care
      will require more than the investigators propose here, but the investigators have already
      plotted the additional steps needed to truly impact patient care. If successful, the data
      gathered in this proposal will lend support to and guide development of a definitive
      randomized trial.
    

Eligibility criteria:

        Inclusion Criteria

          1. Newly diagnosed triple negative breast cancer (TNBC) clinical stage Ic, II, or III

               -  ER and PR < 10%

               -  HER2 negative based on one of the following:

                    -  IHC 0 or 1+

                    -  IHC 2+ and FISH negative

                    -  IHC 2+ and FISH equivocal and no indication for HER2 targeted therapy based
                       on the treating investigators discretion (i.e., HER2: CEP17 ratio < 2.0 or
                       HER2 total copy number <6)

          2. Planned neoadjuvant treatment with anthracycline and taxane containing chemotherapy

          3. ≥ 18 years old at the time of informed consent

          4. ECOG Performance Status 0-1

          5. Ability to provide written informed consent and HIPAA authorization

          6. Women of childbearing potential definition must have a negative pregnancy test within
             14 days of registration. All women (regardless of sexual orientation, having undergone
             a tubal ligation, or remaining celibate by choice) are considered to have childbearing
             potential unless they meet one of the following criteria:

               -  Prior hysterectomy or bilateral oophorectomy;

               -  Has not had menses at any time in the preceding 24 consecutive months

          7. Adequate organ function for anthracycline and taxane based therapy

               -  LVEF > LLN based on cardiac ECHO or MUGA

               -  Hgb > 8.5

               -  ANC > 1,000

               -  Platelets > 100,000

               -  Creatinine < 1.5

               -  T. bili < 1.3

               -  AST < 2.5 x ULN

        Exclusion Criteria

          1. Use of prescription PPIs within 12 months prior to study entry [Dexlansoprazole
             (Dexilant), Pantoprazole (Protonix), Rabeprazole (Aciphex), Esomeprazole (Nexium),
             Lansoprazole (Prevacid), Omeprazole (Prilosec, Zegerid)]

          2. Use of OTC PPIs within 6 months prior to study entry [Esomeprazole (Nexium),
             Lansoprazole (Prevacid), Omeprazole (Prilosec, Zegerid)]

          3. Use of Orlistat or any other known FASN inhibitor within 6 months prior to study entry

          4. Nursing mothers are excluded

          5. Known hypersensitivity to any component of the formulation or substituted
             benzimidazoles

          6. Prior osteoporotic fracture