Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy

NCT02595372 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IUSCC-0555
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Cancer of the Breast

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Pathological Complete Response (pCR) in Patients Who Have Fatty Acid Synthase (FASN) Expression

  pCR is defined as no invasive disease in the breast of axilla at the time of definitive surgery. A patient is considered to have FASN expression if the positivity was \>= 15% at the baseline or after 4-7 days of Omeprazole monotherapy. FASN expression is evaluated using immunohistochemistry in core biopsy samples. The percent of patients with FASN expression that have pCR will be calculated with an exact 95% confidence interval.

  Up to 6 months

Secondary Outcomes (5)

• Percentage of Patients With Pathological Complete Response (pCR) in All Patients

  Up to 6 months

• Percent of Patients With FASN Expression

  up to 1 week

• FASN Positivity Expression at Baseline and After 4-7 Days of Omeprazole Treatment

  baseline and after 4-7 days

• FASN Activity at Baseline and After 4-7 Days of Omeprazole Treatment

  baseline and after 4-7 days

• Number of Patients With Treatment Related Adverse Events Grade 3 or Above

  up to 8 months

Study Arms (1)

High dose omeprazole treatment

EXPERIMENTAL

Patients will be treated with omeprazole 80 mg orally BID beginning 4-7 days prior to chemotherapy and continuing until surgery.

Drug: Omeprazole

Interventions

Omeprazole DRUG

High dose omeprazole treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Planned neoadjuvant treatment with anthracycline and taxane containing chemotherapy
• ≥ 18 years old at the time of informed consent
• ECOG Performance Status 0-1
• Ability to provide written informed consent and HIPAA authorization
• 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
• Adequate organ function for anthracycline and taxane based therapy
• LVEF \> LLN based on cardiac ECHO or MUGA

You may not qualify if:

• 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

Sponsors & Collaborators

• Kathy Miller: lead

Study Sites (9)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Washington Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Indiana University Health North Hospital

Carmel, Indiana, 46032, United States

Location

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Spring Mill Medical Center

Indianapolis, Indiana, 46290, United States

Location

Franklin Square Medical Center

Baltimore, Maryland, 21237, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Omeprazole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Kathy Miller
• Organization: IndianaU

kathmill@iu.edu

(317) 948-3855

Study Officials

• Kathy Miller, MD

  Professor of Medicine, Ballve' Lantero Scholar

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Ballve' Lantero Scholar

Study Record Dates

• First Submitted: November 2, 2015
• First Posted: November 3, 2015
• Study Start: November 12, 2015
• Primary Completion: November 21, 2019
• Study Completion: March 1, 2021
• Last Updated: December 15, 2021
• Results First Posted: June 19, 2020

Record last verified: 2021-12

Locations

US (9)