NCT02595372

Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (actual)
• Sponsor: Kathy Miller · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Primary Objective • Estimate the rate of pathologic complete response (pCR) in patients with triple negative breast cancer and FASN expression treated with standard neoadjuvant chemotherapy (NAC) in combination with high dose omeprazole. Secondary Objectives * Quantify the number of patients with newly diagnosed TNBC with tumors that express FASN. * Estimate the rate of pCR in patients with triple negative breast cancer (irrespective of FASN status) treated with standard NAC in combination with high dose omeprazole. * Describe the safety of incorporating high dose omeprazole with standard NAC. * Estimate the biologic activity of high dose omeprazole in modulating FASN expression and activity. This is a single arm Phase II study. Patients should begin therapy within 7 working days of study entry. Patients will be treated with omeprazole 80 mg orally twice a day (BID) beginning 4-7 days prior to chemotherapy and continuing until surgery. After the brief period of omeprazole monotherapy, patients will begin standard neoadjuvant chemotherapy with doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) for 4 cycles followed by paclitaxel (80 mg/m2) weekly x 12. Doxorubicin and cyclophosphamide (AC) may be administered on a classical every 3 week or dose dense every 2 week (with growth factor support) schedule at the treating physician's discretion. Routine incorporation of carboplatin is not recommended, however use of carboplatin (AUC 6 on week 1, 4, 7, and 10) with paclitaxel is allowed at the treating investigator's discretion. Chemotherapy will be adjusted based on toxicity according to standard treatment guidelines. Patients with overt disease progression during AC should move immediately to paclitaxel therapy. Patients with disease progression during paclitaxel should proceed immediately to surgery.

Conditions

• Cancer of the Breast

Interventions

Type	Name	Description
DRUG	Omeprazole

Timeline

• Start date: 2015-11-12
• Primary completion: 2019-11-21
• Completion: 2021-03-01
• First posted: 2015-11-03
• Last updated: 2021-12-15
• Results posted: 2020-06-19

Locations

9 sites across 1 country: United States

Regulatory

• FDA-regulated drug study