Neoadjuvant Chemotherapy for Operable Premenopausal Breast Cancer Patients

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.

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer Nos Premenopausal
• Intervention / Treatment: Drug: Docetaxel; Drug: epirubicin; Procedure: Modified radical mastectomy or breast-conserving Surgery; Drug: Docetaxel (post-operative); Drug: Epirubicin (post-operative); Radiation: Radiation therapy; Drug: Herceptin （post-operative); Drug: Tamoxifen (post-operative); Drug: cyclophosphamide; Drug: Cyclophosphamide (post-operative)

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fengxi Su, M.D.; Phone Number: 86-20-34071156; Email: fengxisu@vip.163.com

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Recruiting
      • The First People's Hospital of Foshan
      • Contact: Jie Yang; Phone Number: 86-13902805191
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Siyu Wang; Phone Number: 86-18688464714
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: Zhuanghong Wu; Phone Number: 86-13602722502
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • The Third Affiliated Hospital of Sun Yat-sen University
      • Contact: Renbin Liu; Phone Number: 86-13570073298
    • Guangzhou, Guangdong, China, 510260
      • Recruiting
      • the Second Affiliated Hospital of Guangzhou Medical University
      • Contact: Lehong Zhang; Phone Number: 86-13719150959
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • The First Affiliated Hospital of Jinan University
      • Contact: Ningxia Wang; Email: Twnx@Jnu.edu.cn
    • Guangzhou, Guangdong, China, 510010
      • Recruiting
      • Guangdong Women and Children Hospital
      • Contact: Antai Zhang; Phone Number: 86-13925115929
    • Guangzhou, Guangdong, China, 510010
      • Recruiting
      • Guangzhou Army General Hospital
    • Guangzhou, Guangdong, China, 510095
      • Recruiting
      • Tumor Hospital of Guangzhou
      • Contact: Hongsheng Li; Phone Number: 86-13725111258
    • Guangzhou, Guangdong, China, 510100
      • Recruiting
      • The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
      • Contact: Pengxi Liu; Phone Number: 86-13560333752
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
      • Contact: Fengxi Su; Email: fengxisu@vip.163.com
    • Guangzhou, Guangdong, China, 510180
      • Recruiting
      • Guangzhou Women and Children Hospital
    • Guangzhou, Guangdong, China, 510180
      • Recruiting
      • The first People's Hospital of Guangzhou
      • Contact: Li Zhao; Email: gdzhaoli@163.com
    • Guangzhou, Guangdong, China, 510282
      • Recruiting
      • Zhujiang Hospital of Nanfang Medical University
      • Contact: Aiguo Wu; Email: wagtyz@sina.com
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital of Nanfang Medical University
      • Contact: Changsheng Ye; Phone Number: 86-13802954097
    • Shenzhen, Guangdong, China, 518020
      • Recruiting
      • ShenZhen People's Hospital
      • Contact: Dongxian Zhou; Phone Number: 86-13510363636
    • Shenzhen, Guangdong, China, 518035
      • Recruiting
      • The First Affiliated Hospital of Shenzhen University
      • Contact: Xianming Wang; Phone Number: 86-13500056238

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. The patients signed the written informed consent.
2. The patients present with operable breast cancers that were diagnosed by histopathology and have no distant metastasis.
3. The patients have no history of anti-cancer therapies including chemotherapy, radiation therapy, hormone therapy and surgical therapy.
4. The patients have normal cardiac functions by echocardiography.
5. The patients' ECOG scores are ≤ 0-2.
6. The age of patient is ≥ 18 years old; And the patients are premenopausal females.
7. The patients are disposed to practice contraception during the whole trial.

8. 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:

1. 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.
2. The patients have active infections that were not suitable for chemotherapy.
3. The patients have severe non-cancerous diseases.
4. The patients are undergoing current administration of anti-cancer therapies, or are attending some other clinical trails.
5. The patients whose breast cancers are HER2 positive and choose to undergo the neoadjuvant chemotherapy that includes herceptin regimen.
6. The patients are pregnant or lactational, or they refuse to practice contraception during the whole trial.
7. The patients are in some special conditions that they can't understand the written informed consent, such as they are demented or hawkish.
8. The patients have allergic history of the chemotherapeutic agents.
9. The patients have bilateral breast cancers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Study Chair: Fengxi Su, M.D., Sun Yat-Sen Memerial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: December 29, 2011
• First Submitted That Met QC Criteria: January 3, 2012
• First Posted (Estimate): January 4, 2012

Study Record Updates

• Last Update Posted (Estimate): May 24, 2016
• Last Update Submitted That Met QC Criteria: May 23, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant chemotherapy; amenorrhea
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Docetaxel; Cyclophosphamide; Trastuzumab; Epirubicin; Tamoxifen
• Other Study ID Numbers: BCSCO001