Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Taxane

Tubulin Modulators

Antimitotic Agents

weekly Paclitaxel chemotherapy at the dose of 100 mg/m2/week for 8 weeks as a 1-hour infusion and AC/EC (60/600 or 90/600) / 3 weekly.

weekly Paclitaxel at 100mg /m2/week + weekly Carboplatin AUC-2 as an infusion over 60 minutes and AC/EC (60/600 or 90/600)/ 3 weekly.

Platinum based chemotherapy against the standard taxane based chemotherapy in the neo- adjuvant setting

Paclitaxel + Carboplatin

Paclitaxel only

Triple-negative breast cancer is a subtype of breast cancer that is clinically negative for expression of estrogen and progesterone receptors (ER/PR) 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 and/or 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.

The study will test platinum based chemotherapy against the standard taxane based chemotherapy in the neo adjuvant setting as below:

Arm A: Paclitaxel (weekly \*8) + AE/EC 3 weekly \*4 followed by Surgery + RT Arm B: Paclitaxel+ Carboplatin (weekly \*8) + AE/EC 3 weekly \*4 followed by Surgery+ RT

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

Clinical response evaluation during and at the end of Neo-adjuvant Chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT03168880	Triple Negative...	Paclitaxel + Ca... Paclitaxel only	18 Years - 70 Years	Tata Memorial Hospital
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	NCT03168880	Triple Negative...	Paclitaxel + Ca... Paclitaxel only	18 Years - 70 Years	Tata Memorial Hospital

Spots Global Cancer Trial Database for paclitaxel only