Weekly Paclitaxel and Cisplatin to Treat Hormone Receptor Positive and Triple Negative Breast Cancer Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Tubular Breast Cancer, Mucinous Breast Cancer, Invasive Ductal Breast Cancer, Inflammatory Breast Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Cisplatin
* Drug: Gonadotropin-releasing hormone agonist
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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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 >6.0. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemotherapy only<br>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 | Drug: Paclitaxel<br> <br> * Other names: Taxol;Drug: Cisplatin<br> <br> |
| Experimental: GnRHa<br>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 | Drug: Paclitaxel<br> <br> * Other names: Taxol;Drug: Cisplatin<br> <br> Drug: Gonadotropin-releasing hormone agonist<br>* Goserelin 3.6 mg q28d or Leuprolide 11.25 mg q3m<br>|
| Experimental: letrozole<br>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 | Drug: Paclitaxel<br> <br> * Other names: Taxol;Drug: Cisplatin<br> <br> Drug: Letrozole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete remission rate | Pathological complete remission is defined as no invasive cancer in breast and axillary nodes. | after 4 months preoperative treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Drug Related Treatment Adverse Events | Adverse events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. | 4 months during neoadjuvant therapy | 
| Clinical and imaging response | To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment | 4 months during treatment | 
| disease free survival (DFS) | DFS is defined as the time in months from randomization until first occurrence of locoregional recurrence, distant metastasis, contralateral breast cancer, second primary tumor, or death from any cause. | 5 years | 
| regional recurrence free survival (RRFS) | RRFS is defined as the time period between registration and first event | 5 years | 
| local recurrence free survival (LRFS) | LRFS is defined as the time period between registration and first event | 5 years | 
| overall survival (OS) | OS is defined as the time period between registration and first event | 5 years | 
| distant-disease- free survival (DDFS) | DDFS is defined as the time period between registration and first event | 5 years | 
| rate of tumor remission （RTR） | RTR is defined as the proportion of tumor remission per unit time | after 2 cycles and 4 cycles during neoadjuvant therapy | 
| serum markers | Changes in the angiogenic serum markers(mirRNA, lncRNA, cirRNA), measured at diagnosis and surgery | Pre-treatment and/or surgical | 
| molecular markers | Pre-treatment and surgical expression of molecular markers （LHRHa receptor, EGFR，PD-L1) | Pre-treatment and/or surgical |