Phase 2
Completed N=42
Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy
Cancer of the Breast
Source: ClinicalTrials.gov NCT02595372 ↗
Enrolled (actual)
42
Serious AEs
11.9%
Results posted
Jun 2020
Primary outcomePrimary: Percentage of Patients With Pathological Complete Response (pCR) in Patients Who Have Fatty Acid Synthase (FASN) Expression — 72.4 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Patients With Pathological Complete Response (pCR) in Patients Who Have Fatty Acid Synthase (FASN) Expression |
72.4 | — |
| SECONDARY Percentage of Patients With Pathological Complete Response (pCR) in All Patients |
74.4 | — |
| SECONDARY Percent of Patients With FASN Expression |
93.3 | — |
| SECONDARY FASN Positivity Expression at Baseline and After 4-7 Days of Omeprazole Treatment |
53.9; 41.7 | — |
| SECONDARY FASN Activity at Baseline and After 4-7 Days of Omeprazole Treatment |
2.1; 1.3 | — |
| SECONDARY Number of Patients With Treatment Related Adverse Events Grade 3 or Above |
— | — |
Eligibility Criteria
Inclusion Criteria
- Newly diagnosed triple negative breast cancer (TNBC) clinical stage Ic, II, or III
- ER and PR 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
- Use of prescription PPIs within 12 months prior to study entry [Dexlansoprazole (Dexilant), Pantoprazole (Protonix), Rabeprazole (Aciphex), Esomeprazole (Nexium), Lansoprazole (Prevacid), Omeprazole (Prilosec, Zegerid)]
- Use of OTC PPIs within 6 months prior to study entry [Esomeprazole (Nexium), Lansoprazole (Prevacid), Omeprazole (Prilosec, Zegerid)]
- Use of Orlistat or any other known FASN inhibitor within 6 months prior to study entry
- Nursing mothers are excluded
- Known hypersensitivity to any component of the formulation or substituted benzimidazoles
- Prior osteoporotic fracture
Data sourced from ClinicalTrials.gov (NCT02595372). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.