A Prospective, Randomized, Open-label Comparison of Preoperative Weekly Paclitaxel and Cisplatin With or Without Endocrine Therapy in Patients With Operable Hormone Receptor Positive and Triple Negative Locally Advanced Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- Tubular Breast Cancer
- Sponsor
- RenJi Hospital
- Enrollment
- 250
- Locations
- 12
- Primary Endpoint
- pathological complete remission rate
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The investigators hypothesize that paclitaxel combined with cisplatin in a weekly-based regimen as neoadjuvant chemotherapy is effective and tolerable for locally advanced breast cancer.
In patients with some sub-type advanced breast cancer, neo-adjuvant chemotherapy combined with endocrine therapy may improve the pathological remission rate.
Premenopausal patients with triple negative breast caner and hormonal receptor positve breast cancer patients will be randominzed to have neoadjuvant chemotherapy combined with endocrine therapy or not.
Detailed Description
In this trial, patients with ER and or PR positive breast cancer will be separately randomized to have chemotherapy or chemotherapy combined with endocrine therapy according to their menstrual status. Letrozole for the postmenopausal women and ovarian function suppression for the premenopausal women. Patients with triple negative breast cancer will be randomized to have neoadjuvant chemotherapy combined with ovarian function suppression if she is premenopausal. Postermenopausal patients with triple negative breast caner will only have neoadjuvant chemotherapy. Patients with Her2 overexpression can obtain anti-Her2 target therapy. This study has been amended to a 1:2 ratio to control and neoadjuvant chemotherapy combination of endocrine therapy.
Investigators
Jinsong Lu
professor
RenJi Hospital
Eligibility Criteria
Inclusion Criteria
- •Women aged ≥18years and ≤70 years;
- •At least on measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). Histologically confirmed invasive breast cancer, tumor size ≥2 cm, T2-4 N0-3M0;
- •ER/PR/HER-2 and Ki-67 status detected on core biopsy. ER and/or PR positive was defined as \>1% stained cells.HER2-positive is defined as immuno-histochemistry (IHC) 3+ or the ratio of HER2 gene signals to chromosome 17 signals \>2.0 or HER2 gene copy \>6.
- •No prior systemic or loco-regional treatment of breast cancer;
- •Adequate bone marrow function:WBC≥4.0×109/L, Absolute neutrophil count（ANC）≥1.5×109/L, Platelets（PLT）≥100×109/L, Hemoglobin（Hb）≥90g/L;aspartate aminotransferase(AST),Alanine aminotransferase (ALT)≤1.5 upper normal limit (UNL), creatinine≤1.5 UNL, bilirubin≤1.5UNL;
- •No obvious main organs dysfunction.
Exclusion Criteria
- •Unwilling or unable to use an acceptable method of contraception in 8 weeks (including 8 weeks) after final dose of test drug;
- •Patient is pregnant or breast feeding;
- •Inflammatory breast cancer and metastatic breast cancer;
- •Any evidence of sense or motor nerve disorders;
- •Patients with medical conditions taht indicate intolerant to neoadjuvant therapy, including uncontrolled cardiovascular disease, severe infection;
- •Any concurrent malignancy other than breast cancer;
- •Know severe hypersensitivity to any drugs in this study.
Arms & Interventions
Chemotherapy only
Paclitaxel injection 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle；Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle； for 4 cycles
Intervention: Paclitaxel
Chemotherapy only
Paclitaxel injection 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle；Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle； for 4 cycles
Intervention: Cisplatin
GnRHa
Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Gonadotropin-releasing hormone agonist （GnRHa）11.25 mg every 3 months or 3.6mg every month subcutaneously
Intervention: Paclitaxel
GnRHa
Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Gonadotropin-releasing hormone agonist （GnRHa）11.25 mg every 3 months or 3.6mg every month subcutaneously
Intervention: Cisplatin
GnRHa
Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Gonadotropin-releasing hormone agonist （GnRHa）11.25 mg every 3 months or 3.6mg every month subcutaneously
Intervention: Gonadotropin-releasing hormone agonist
letrozole
Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Letrozole 2.5mg/day
Intervention: Paclitaxel
letrozole
Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Letrozole 2.5mg/day
Intervention: Cisplatin
letrozole
Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Letrozole 2.5mg/day
Intervention: Letrozole
Outcomes
Primary Outcomes
pathological complete remission rate
Time Frame: after 4 months preoperative treatment
Pathological complete remission is defined as no invasive cancer in breast and axillary nodes.
Secondary Outcomes
- local recurrence free survival (LRFS)(5 years)
- overall survival (OS)(5 years)
- rate of tumor remission （RTR）(after 2 cycles and 4 cycles during neoadjuvant therapy)
- disease free survival (DFS)(5 years)
- regional recurrence free survival (RRFS)(5 years)
- serum markers(Pre-treatment and/or surgical)
- Number of Participants With Drug Related Treatment Adverse Events(4 months during neoadjuvant therapy)
- distant-disease- free survival (DDFS)(5 years)
- Clinical and imaging response(4 months during treatment)
- molecular markers(Pre-treatment and/or surgical)