Cancer of the BreastPhase 2NCT02595372
Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy
A Phase 2 study testing Omeprazole in people with Cancer of the Breast, run by Kathy Miller at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of the Breast
- What is being tested?
- Omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 9 sitesUnited States
- Study dates
- 12 Nov 2015to 1 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 21Show fewer
- 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
- Hgb > 8.5
- ANC > 1,000
- Platelets > 100,000
- Creatinine < 1.5
- T. bili < 1.3
- AST < 2.5 x ULN
Who cannot join
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Franklin Square Medical Center
Baltimore, Maryland, 21237
Indiana University Health North Hospital
Carmel, Indiana, 46032
Ohio State University
Columbus, Ohio, 43210
Indiana University Health Hospital
Indianapolis, Indiana, 46202
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Spring Mill Medical Center
Indianapolis, Indiana, 46290
Georgetown University
Washington D.C., District of Columbia, 20007
Washington Hospital
Washington D.C., District of Columbia, 20010
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
About this study
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.
Read the 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
- Being tested
- Omeprazole
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmeprazoleDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 6 months
Secondary outcomes (5)
Percentage of Patients With Pathological Complete Response (pCR) in All Patients
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.
Measured: Up to 6 months
Percent of Patients With FASN Expression
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.
Measured: up to 1 week
FASN Positivity Expression at Baseline and After 4-7 Days of Omeprazole Treatment
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.
Measured: baseline and after 4-7 days
FASN Activity at Baseline and After 4-7 Days of Omeprazole Treatment
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.
Measured: baseline and after 4-7 days
Number of Patients With Treatment Related Adverse Events Grade 3 or Above
Number of unique patients who had an Omeprazole treatment related (possible, probable or definite) adverse event with grade >= 3.
Measured: up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study start12 Nov 2015
- Primary completion21 Nov 2019
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cancer of the BreastStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kathy Miller
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kathy Miller, Indiana University
- Investigators
- Kathy Miller, MD, Principal investigator, Professor of Medicine, Ballve' Lantero Scholar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02595372
- Sponsor's protocol ID
- IUSCC-0555
- Status last verified
- Dec 2021
- First submitted
- 2 Nov 2015
- Last updated
- 15 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT02595372
- Acronym / sponsor ID
- IUSCC-0555
- Conditions
- Cancer of the Breast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Kathy MillerUniversity, hospital or other
- Study start
- 12 Nov 2015 (actual)
- Primary completion
- 21 Nov 2019 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Posted 19 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High dose omeprazole treatment | Experimental | Drug: OmeprazolePatients will be treated with omeprazole 80 mg orally BID beginning 4-7 days prior to chemotherapy and continuing until surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Newly diagnosed triple negative breast cancer (TNBC) clinical stage Ic, II, or III
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omeprazole | Drug | High dose omeprazole treatment |
Primary outcome
Percentage of Patients With Pathological Complete Response (pCR) in Patients Who Have Fatty Acid Synthase (FASN) Expression
Time frame: 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.
5 secondary outcomes
Percentage of Patients With Pathological Complete Response (pCR) in All Patients
Time frame: Up to 6 months
Percent of Patients With FASN Expression
Time frame: up to 1 week
FASN Positivity Expression at Baseline and After 4-7 Days of Omeprazole Treatment
Time frame: baseline and after 4-7 days
FASN Activity at Baseline and After 4-7 Days of Omeprazole Treatment
Time frame: baseline and after 4-7 days
Number of Patients With Treatment Related Adverse Events Grade 3 or Above
Time frame: up to 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy Miller, MD principal investigator
Professor of Medicine, Ballve' Lantero Scholar
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omeprazole in people with Cancer of the Breast, run by Kathy Miller at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Pathological Complete Response (pCR) in Patients Who Have Fatty Acid Synthase (FASN) Expression (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2021.