Neoadjuvant Chemotherapy for Operable Premenopausal Breast Cancer Patients

Study Overview
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Brief Summary
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The current study is a multicentre, randomized, open (unblended), prospective clinical trial which is sponsored by the researchers. The trial is designed to compare the effectiveness between docetaxel plus epirubicin, and docetaxel plus epirubicin plus cyclophosphamide as neoadjuvant chemotherapy for operable premenopausal breast cancer patients, and also to compare the outcomes associated with chemo-induced amenorrhea between the two neoadjuvant chemotherapies. The investigators will randomly assign 600 premenopausal female patients with operable breast cancer to receive four cycles of docetaxel and epirubicin (TE); or four cycles of docetaxel, epirubicin, and cyclophosphamide (TEC). After every two cycles of neoadjuvant chemotherapy, the investigators will estimate the effectiveness of therapy. Patients will undergo modified radical mastectomy or breast-conserving surgery after four cycles of neoadjuvant chemotherapy, and then receive postoperative chemotherapy (two cycles), radiation therapy, herceptin targeted therapy or hormone therapy according to the NCCN (2011) guideline. The follow-up will be ten years after surgeries. The primary aim is to examine whether the docetaxel and epirubicin (TE) will be as effective as the docetaxel, epirubicin, and cyclophosphamide (TEC) (pCR rate, cCR rate, PR rate, SD rate, progression-free survival (PFS) and overall survival (OS)). The secondary aim is to correlate chemo (TE/TEC)-induced amenorrhea with outcomes in premenopausal women.

Official Title
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Comparison of the Effectiveness of Neoadjuvant Chemotherapy and the Outcomes Associated With Chemo-induced Amenorrhea Between Docetaxel Plus Epirubicin, and Docetaxel Plus Epirubicin Plus Cyclophosphamide as Neoadjuvant Chemotherapy for Operable Premenopausal Breast Cancer Patients.

Conditions
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Breast Cancer Nos Premenopausal

Intervention / Treatment
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* Drug: Docetaxel
* Drug: epirubicin
* Drug: cyclophosphamide
* Procedure: Modified radical mastectomy or breast-conserving Surgery
* Drug: Docetaxel (post-operative)
* Drug: Epirubicin (post-operative)
* Drug: Cyclophosphamide (post-operative)
* Radiation: Radiation therapy
* Drug: Herceptin （post-operative)
* Drug: Tamoxifen (post-operative)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients signed the written informed consent. The patients present with operable breast cancers that were diagnosed by histopathology and have no distant metastasis. The patients have no history of anti-cancer therapies including chemotherapy, radiation therapy, hormone therapy and surgical therapy. The patients have normal cardiac functions by echocardiography. The patients' ECOG scores are ≤ 0-2. The age of patient is ≥ 18 years old; And the patients are premenopausal females. The patients are disposed to practice contraception during the whole trial. The results of patients' blood tests are as follows: Hb ≥ 90 g/L WBC ≥ 4.0×109/L Plt ≥ 100×109/L Neutrophils ≥ 1.5×109/L ALT and AST ≤ triple of normal upper limit. TBIL ≤ 1.5 times of normal upper limit. Creatinine ≤ 1.25 times of normal upper limit. Exclusion Criteria: The patients have other cancers at the same time or have the history of other cancers in recent five years, excluding the controlled skin basal cell carcinoma or skin squamous cell carcinoma or carcinoma in situ of cervix. The patients have active infections that were not suitable for chemotherapy. The patients have severe non-cancerous diseases. The patients are undergoing current administration of anti-cancer therapies, or are attending some other clinical trails. The patients whose breast cancers are HER2 positive and choose to undergo the neoadjuvant chemotherapy that includes herceptin regimen. The patients are pregnant or lactational, or they refuse to practice contraception during the whole trial. The patients are in some special conditions that they can't understand the written informed consent, such as they are demented or hawkish. The patients have allergic history of the chemotherapeutic agents. The patients have bilateral breast cancers.

Ages Eligible for Study
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Minimum Age: 18 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: Docetaxel plus epirubicin<br> | Drug: Docetaxel<br>* 75mg/m2, iv injection, day1, every 21 days<br>Drug: epirubicin<br>* 80mg/ m2, iv injection, day1, every 21 days<br>Procedure: Modified radical mastectomy or breast-conserving Surgery<br>* Two weeks after four cycles of neoadjuvant chemotherapy<br>Drug: Docetaxel (post-operative)<br>* Two weeks after surgery,75mg/m2, iv injection, day1, every 21 days, 4 cycles totally.<br>Drug: Epirubicin (post-operative)<br>* Two weeks after surgery, 80mg/m2,iv injection, day1, every 21 days, 4 cycles totally<br>Radiation: Radiation therapy<br>* Two weeks after post-operative chemotherapy, perform radiation therapy based on 2011 NCCN guideline.<br>Drug: Herceptin （post-operative)<br>* Perform herceptin therapy (one year) based on 2011 NCCN guideline if the pathological test of the operative tumor sample showed HER2 positive.<br>Drug: Tamoxifen (post-operative)<br>* After radiation therapy, totally five years. Perform hormone therapy based on 2011 NCCN guideline if the tumor is ER/PR positive.<br>|
| Active Comparator: docetaxel plus epirubicin plus cyclophosphamide<br> | Drug: Docetaxel<br>* 75mg/m2, iv injection, day1, every 21 days<br>Drug: epirubicin<br>* 80mg/ m2, iv injection, day1, every 21 days<br>Drug: cyclophosphamide<br>* 500 mg/m2, iv injection, day1, every 21 days<br>Procedure: Modified radical mastectomy or breast-conserving Surgery<br>* Two weeks after four cycles of neoadjuvant chemotherapy<br>Drug: Docetaxel (post-operative)<br>* Two weeks after surgery,75mg/m2, iv injection, day1, every 21 days, 4 cycles totally.<br>Drug: Epirubicin (post-operative)<br>* Two weeks after surgery, 80mg/m2,iv injection, day1, every 21 days, 4 cycles totally<br>Drug: Cyclophosphamide (post-operative)<br>* Two weeks after surgery, 500mg/m2, iv injection, day1, every 21 days, 4 cycles totally.<br>Radiation: Radiation therapy<br>* Two weeks after post-operative chemotherapy, perform radiation therapy based on 2011 NCCN guideline.<br>Drug: Herceptin （post-operative)<br>* Perform herceptin therapy (one year) based on 2011 NCCN guideline if the pathological test of the operative tumor sample showed HER2 positive.<br>Drug: Tamoxifen (post-operative)<br>* After radiation therapy, totally five years. Perform hormone therapy based on 2011 NCCN guideline if the tumor is ER/PR positive.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival of patients. |  | within 10 years after diagnosis | 
| Overall survival of the patients |  | within 10 years after diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pathological remission rate of patients after neoadjuvant chemotherapy. |  | within 80 days after diagnosis (after 4 cycles of neoadjuvant chemotherapy) | 
| The clinical remission rate of patients after neoadjuvant chemotherapy |  | within 80 days after diagnosis (after 4 cycles of neoadjuvant chemotherapy) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, neoadjuvant chemotherapy, amenorrhea