Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy

• Status: Completed
• Trial end date: 2021-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kathy Miller
• Treatments: Omeprazole

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