Ignite Creation Date:
2024-06-16 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06452394
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-03
First Post:
2024-06-05
Brief Title:
NEODOXy Targeting Breast Cancer Stem Cells With Doxycycline
Sponsor:
Swiss Group for Clinical Cancer Research
Organization:
Swiss Group for Clinical Cancer Research
Study Overview
Official Title:
NEODOXy Targeting Cancer Stem Cells With NEOadjuvant DOXYcycline in Patients With Early Estrogen Receptor Positive Human Epidermal Growth Factor Receptor 2- Negative Breast Cancer A Prospective Multicenter Single Arm Open Label Phase II Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
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:
Despite modern surgical and medical treatments breast cancer can re-occur and lead 20 of patients to death During the last 20 years pre-clinical studies have shown that treatment failures may be due to the presence of a sub-type of cancer cells the cancer stem cells which are resistant to chemotherapy and radiotherapy By chance doxycycline an old inexpensive and safe molecule seems to target effectively these cancer stem cells This study proposes to check for the clinical efficacy of doxycycline to target the cancer stem cells and improve the response to neoadjuvant chemotherapy in ERHER2- breast cancers
Detailed Description:
Patients with early stage ERHER2- breast cancer BC have a low pathologic complete response pCR rate of less than 15 Over the past 20 years studies have identified a subset of cancer cells with tumorigenic and stem-like properties known as cancer stem cells CSCs that are involved in tumour initiation metastasis relapse and resistance to treatment Cancer cells with stem-like properties are known to possess cellular plasticity that not only enables self-renewal capacity but also exhibits high tumourigenic potential and resistance to oncological therapies such as chemotherapy andor radiotherapy
CSCs can arise from normal adult breast stem cells through mutations or directly from differentiated tumor cells Tumour hypoxia has been shown to be one of the major factors promoting and maintaining the stemness phenotype The metabolism of CSCs in hypoxia relies on a delicate balance between reduced energy requirements through reduced proliferation and an altered balance between mitochondrial oxidative phosphorylation OXPHOS and cytosolic glycolysis while maintaining mitochondrial redox homeostasis to control reactive oxygen species ROS levels Any slight imbalance in mitochondrial redox homeostasis in CSCs leading to transient effects on ROS may promote their differentiation towards their non-stem tumour cell counterparts Consequently specific drugs targeting mitochondrial metabolism leading to increased ROS levels may destabilise CSCs
This study proposes to check for the clinical efficacy of doxycycline to target the cancer stem cells and improve the response to neoadjuvant chemotherapy in ERHER2- breast cancers The change in the stemness marker ALDH1 assessed before and after treatment and the effect of doxycycline on the pathological response will be studied
The translational work will be to better define these stem cells and to grow organoid cultures to study the effects of the different drugs in vitro This study also aims to address a number of translational research questions using a tumor sample obtained from an additional core biopsy prior to treatment initiation and using a fresh tumor sample from the surgical specimen in the case of residual tumor after neoadjuvant treatment
Quantify and characterise the effects of doxycycline on tumors
Identify factors that facilitate or prevent the effects of doxycycline
Estimate the effect of doxycycline compared to other CSC-targeting drugs
CSCs can arise from normal adult breast stem cells through mutations or directly from differentiated tumor cells Tumour hypoxia has been shown to be one of the major factors promoting and maintaining the stemness phenotype The metabolism of CSCs in hypoxia relies on a delicate balance between reduced energy requirements through reduced proliferation and an altered balance between mitochondrial oxidative phosphorylation OXPHOS and cytosolic glycolysis while maintaining mitochondrial redox homeostasis to control reactive oxygen species ROS levels Any slight imbalance in mitochondrial redox homeostasis in CSCs leading to transient effects on ROS may promote their differentiation towards their non-stem tumour cell counterparts Consequently specific drugs targeting mitochondrial metabolism leading to increased ROS levels may destabilise CSCs
This study proposes to check for the clinical efficacy of doxycycline to target the cancer stem cells and improve the response to neoadjuvant chemotherapy in ERHER2- breast cancers The change in the stemness marker ALDH1 assessed before and after treatment and the effect of doxycycline on the pathological response will be studied
The translational work will be to better define these stem cells and to grow organoid cultures to study the effects of the different drugs in vitro This study also aims to address a number of translational research questions using a tumor sample obtained from an additional core biopsy prior to treatment initiation and using a fresh tumor sample from the surgical specimen in the case of residual tumor after neoadjuvant treatment
Quantify and characterise the effects of doxycycline on tumors
Identify factors that facilitate or prevent the effects of doxycycline
Estimate the effect of doxycycline compared to other CSC-targeting drugs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None