Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy



Status:Recruiting
Conditions:Breast Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:3/2/2019
Start Date:November 12, 2015
End Date:December 31, 2019
Contact:Cheri West, RN
Email:chawest@iupui.edu
Phone:317-278-3021

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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.

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.

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
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Indianapolis, Indiana 46202
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Baltimore, Maryland 21237
Principal Investigator: Filipa Lynce, MD
Phone: 202-784-3923
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Carmel, Indiana 46032
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281 W. Lane Ave
Columbus, Ohio 43210
(614) 292-6446
Principal Investigator: Sagar Sardesai, MD
Phone: 314-685-6046
Ohio State University The Ohio State University’s main Columbus campus is one of America’s largest...
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Indianapolis, Indiana 46202
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Indianapolis, Indiana 46290
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3700 O St NW
Washington, District of Columbia 20057
(202) 687-0100
Principal Investigator: Filipa Lynce, MD
Phone: 202-784-3923
Georgetown University Georgetown University is one of the world's leading academic and research institutions, offering...
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Washington, District of Columbia 20010
Principal Investigator: Filipa Lynce, MD
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Winston-Salem, North Carolina 27157
Principal Investigator: Alexandra Thomas, MD
Phone: 336-713-6927
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