Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy
- Registration Number
- NCT02595372
- Lead Sponsor
- Kathy Miller
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description High dose omeprazole treatment Omeprazole Patients will be treated with omeprazole 80 mg orally BID beginning 4-7 days prior to chemotherapy and continuing until surgery.
- Primary Outcome Measures
Name Time Method Percentage of Patients With Pathological Complete Response (pCR) in Patients Who Have Fatty Acid Synthase (FASN) Expression Up to 6 months 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.
- Secondary Outcome Measures
Name Time Method FASN Activity at Baseline and After 4-7 Days of Omeprazole Treatment baseline and after 4-7 days The mean and standard deviation of FASN activity determined at baseline and after 4-7 days of Omeprazole treatment. FASN activity was evaluated using immunohistochemistry in core biopsy samples.
Percentage of Patients With Pathological Complete Response (pCR) in All Patients Up to 6 months pCR is defined as no invasive disease in the breast or axilla at the time of definitive surgery. The percentage of patients who achieve pCR along with exact 95% confidence intervals were calculated.
Percent of Patients With FASN Expression up to 1 week FASN expression was evaluated using immunohistochemistry in core biopsy samples. FASN expression was determined if the positivity was \>= 15%. The percent of patients who had FASN expression and the exact 95% confidence intervals were calculated.
FASN Positivity Expression at Baseline and After 4-7 Days of Omeprazole Treatment baseline and after 4-7 days The mean and standard deviation of FASN positivity expression determined at baseline and after 4-7 days of Omeprazole treatment. FASN expression is evaluated using immunohistochemistry in core biopsy samples.
Number of Patients With Treatment Related Adverse Events Grade 3 or Above up to 8 months Number of unique patients who had an Omeprazole treatment related (possible, probable or definite) adverse event with grade \>= 3.
Trial Locations
- Locations (9)
Indiana University Health North Hospital
🇺🇸Carmel, Indiana, United States
Indiana University Health Hospital
🇺🇸Indianapolis, Indiana, United States
Indiana University Health Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Spring Mill Medical Center
🇺🇸Indianapolis, Indiana, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Washington Hospital
🇺🇸Washington, District of Columbia, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Franklin Square Medical Center
🇺🇸Baltimore, Maryland, United States