Ignite Creation Date:
2024-05-06 @ 10:06 AM
Last Modification Date:
2024-10-26 @ 12:25 PM
Study NCT ID:
NCT03168880
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-22
First Post:
2017-05-20
Brief Title:
A Randomized Controlled Trial of Neoadjuvant Weekly Paclitaxel Versus Weekly Paclitaxel Plus Weekly Carboplatin In Women With Large Operable or Locally Advanced Triple Negative Breast Cancer
Sponsor:
Tata Memorial Hospital
Organization:
Tata Memorial Hospital
Study Overview
Official Title:
A Randomized Controlled Trial of Neoadjuvant Weekly Paclitaxel Versus Weekly Paclitaxel Plus Weekly Carboplatin In Women With Large Operable or Locally Advanced Triple Negative Breast Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
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:
TNBC
Brief Summary:
Triple-negative breast cancer is a subtype of breast cancer that is clinically negative for expression of estrogen and progesterone receptors ERPR and HER2 protein It is characterized by its unique molecular profile aggressive behavior distinct patterns of metastasis and lack of targeted therapies Although not synonymous the majority of triple-negative breast cancers carry the basal-like molecular profile on gene expression arrays
Although sensitive to chemotherapy early relapse is common and these cancers show a predilection for visceral metastasis including brain metastasis Targeted agents including epidermal growth factor receptor EGFR vascular endothelial growth factor VEGF and poly ADP-ribose polymerase PARP inhibitors are currently in clinical trials and hold promise in the treatment of this aggressive disease
Multiple independent data sets have revealed that the triple negative type of breast cancer carries a poor prognosis It is unclear whether the poor prognosis of triple negative breast cancer is due to poor therapy options or inherent aggressiveness Given their triple negative receptor status these tumors are not amenable to conventional targeted therapies for breast cancer such as endocrine therapy or trastuzumab leaving only chemotherapy in the therapeutic armamentarium
Patients on metformin showed a 30-40 protection against all forms of cancer Recent pilot studies carried out using population registries raise the possibility that metformin may reduce cancer risk andor improve cancer prognosis One showed an unexpectedly lower risk of a cancer diagnosis among diabetics using metformin compared with a control group of diabetics using other treatments another showed lower cancer-specific mortality among subjects with diabetes using metformin compared with diabetics on other treatments Metformin is a biguanide known to be an insulin sensitizing agent which promotes reduced circulating insulin and glucose levels in hyper-glycaemic and hyper-insulinaemic patients Metformin activates the AMP dependent kinase attenuates insulin and IGF-1 stimulated proliferation in breast cancer cells and a general decrease in protein synthesis in vitro Western blot analysis indicated that metformin stimulates AMPK phosphorylation in a dose-dependent manner AMPK activation is associated with decreased phosphorylation of mTOR and S6 kinase While metformin reduces breast carcinoma cell proliferation both in vitro and in vivo the activation of AMPK leads to significant VEGF production angiogenesis and tumor progression This must be taken into consideration when it is applied in as a therapeutic regimen
Although sensitive to chemotherapy early relapse is common and these cancers show a predilection for visceral metastasis including brain metastasis Targeted agents including epidermal growth factor receptor EGFR vascular endothelial growth factor VEGF and poly ADP-ribose polymerase PARP inhibitors are currently in clinical trials and hold promise in the treatment of this aggressive disease
Multiple independent data sets have revealed that the triple negative type of breast cancer carries a poor prognosis It is unclear whether the poor prognosis of triple negative breast cancer is due to poor therapy options or inherent aggressiveness Given their triple negative receptor status these tumors are not amenable to conventional targeted therapies for breast cancer such as endocrine therapy or trastuzumab leaving only chemotherapy in the therapeutic armamentarium
Patients on metformin showed a 30-40 protection against all forms of cancer Recent pilot studies carried out using population registries raise the possibility that metformin may reduce cancer risk andor improve cancer prognosis One showed an unexpectedly lower risk of a cancer diagnosis among diabetics using metformin compared with a control group of diabetics using other treatments another showed lower cancer-specific mortality among subjects with diabetes using metformin compared with diabetics on other treatments Metformin is a biguanide known to be an insulin sensitizing agent which promotes reduced circulating insulin and glucose levels in hyper-glycaemic and hyper-insulinaemic patients Metformin activates the AMP dependent kinase attenuates insulin and IGF-1 stimulated proliferation in breast cancer cells and a general decrease in protein synthesis in vitro Western blot analysis indicated that metformin stimulates AMPK phosphorylation in a dose-dependent manner AMPK activation is associated with decreased phosphorylation of mTOR and S6 kinase While metformin reduces breast carcinoma cell proliferation both in vitro and in vivo the activation of AMPK leads to significant VEGF production angiogenesis and tumor progression This must be taken into consideration when it is applied in as a therapeutic regimen
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
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