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

NCT ID: NCT03168880

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 720 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2025-11-30

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

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.

Group Type: ACTIVE_COMPARATOR

Paclitaxel only

Intervention Type: DRUG

B

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.

Group Type: EXPERIMENTAL

Paclitaxel + Carboplatin

Intervention Type: DRUG

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

Interventions

Paclitaxel + Carboplatin

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

Intervention Type: DRUG

Paclitaxel only

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 18-70 years

2. All patients with baseline clinical staging T4, N0-3, M0 or T1-4, N2-3, M0 and T3, N1, M0 with triple negative hormone status.

3. Patients with adequate baseline marrow function defined as ANC > 1500/mm3 and Platelet count > 1, 00,000/mm3.

4. Patients with acceptable liver function tests (normal bilirubin and AST/ALT < 2 times the upper limit of normal) and normal renal function tests at baseline

5. Patients willing to provide informed consent

6. Patients fit for chemotherapy

Exclusion Criteria

1. Prior excision biopsy

2. Metastatic breast cancer

3. Women with inflammatory breast cancer

4. Poor cardiac function at baseline with LVEF <40%

5. Patients with a prior history of a malignancy

6. Pregnant or lactating women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Tata Memorial Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Dr Rajendra A. Badwe

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Tata memorial Centre

Mumbai, Maharashtra, India

Countries

India

Other Identifiers

CTRI/2012/07/002802

Identifier Type: -

Identifier Source: org_study_id