Ignite Creation Date:
2024-05-06 @ 7:46 AM
Last Modification Date:
2024-10-26 @ 11:52 AM
Study NCT ID:
NCT02595372
Status:
COMPLETED
Last Update Posted:
2021-12-15
First Post:
2015-11-02
Brief Title:
Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy
Sponsor:
Kathy Miller
Organization:
Indiana University
Study Overview
Official Title:
Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy
Status:
COMPLETED
Status Verified Date:
2021-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 mgm2 and cyclophosphamide 600 mgm2 for 4 cycles followed by paclitaxel 80 mgm2 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 physicians 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 investigators 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
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 mgm2 and cyclophosphamide 600 mgm2 for 4 cycles followed by paclitaxel 80 mgm2 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 physicians 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 investigators 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None