Sequential Neo-adjuvant Chemotherapy Followed by Capecitabine Vs. Conventional Adjuvant Chemotherapy in Breast Cancer

Breast Neoplasm Female Clinical Trial

— NACVCAC  

Official title:

A Prospective Randomized Controlled Trail to Evaluate Efficacy and Safety of Sequential Neo-adjuvant Chemotherapy Plus Surgery Followed by Capecitabine Versus Conventional Postoperative Adjuvant Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03011060
• Other study ID #: JLUDBSCRH 001
• Status: Recruiting
• Phase: Phase 3
• First received: January 3, 2017
• Last updated: January 8, 2017
• Start date: December 2016
• Est. completion date: February 2025

Study information

• Verified date: January 2017
• Source: First Hospital of Jilin University
• Contact: Fan Zhimin, Professor
• Phone: +8613756661286
• Email: fanzhimn[@]163.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This study evaluates whether sequential neo-adjuvant chemotherapy plus surgery followed by Capecitabine could achieve additional benefits over traditional postoperative chemotherapy. In the study group, patients that do not achieve pathological complete response(pCR) will receive sequential neo-adjuvant chemotherapy followed by Capecitabine. In the control group, patients will be treated with postoperative adjuvant chemotherapy.

Description:

Neo-adjuvant chemotherapy(NAC) is a standard treatment for locally advanced breast cancer(LABC). By down-staging LABC, NAC is able to make inoperable cases operable as well as to make breast conserving surgery an option again for some patients.Neo-adjuvant chemotherapy is more and more widely used in operable breast cancer since it provides critical information on chemotherapy response. However, only 15% to 20% of the patients can benefit from Neo-adjuvant chemotherapy and achieve pCR. Although we obtained the information chemotherapy response for the rest of the patients who received Neo-adjuvant chemotherapy, there are still controversies on how the information will be used for further treatment. Therefore, it is a problem that needs resolving how these patients can benefit from the information Neo-adjuvant chemotherapy provides and whether Neo-adjuvant chemotherapy can replace conventional adjuvant chemotherapy at all. Our study aims to make Neo-adjuvant chemotherapy benefit more patients.

Registered patients in stage Ⅰ- Ⅲ A breast cancer is randomly split into two groups(study group and control group).In the study group, patients achieving pCR will be followed up for 5 years while patients that do not achieve pCR after neo-adjuvant chemotherapy will be treated with Capecitabine for 8 cycles after surgery. On the other hand, patients in the control group will accept surgeries and conventional adjuvant chemotherapies. Follow-up study will last 5 years. DFS and OS will be compared between the two groups.

This study provides an important basis and methods for the further treatment of patients after neo-adjuvant chemotherapy. It discusses whether neo-adjuvant chemotherapy could replace conventional adjuvant chemotherapy and become a new standard for breast cancer treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1588
• Est. completion date: February 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Pathologically confirmed unilateral invasive carcinoma (all pathological types);

2. No gross or microscopic residual tumor after resection;

3. Clinical stage ?-stage ? A, no absolute surgical contraindications;

4. Eastern Cooperative Oncology Group(ECOG) score =1;

5. Accepting adjuvant chemotherapy within 15 days after surgery;

6. No peripheral neuropathy;

7. Normal bone marrow and organ functions:

1. Bone marrow function: ANC=1500/mm3,PLT=100000/mm3,HGB=8g/dl

2. Renal function: serum creatinine=1.5 times the upper limit of normal(ULN), Liver function: total bilirubin =1.5 times the upper limit of normal,AST=2.5 times the upper limit of normal,alanine aminotransferase(ALT)=2.5 times the upper limit of normal

3. Cardiac function:LVEF=50%

8. Signed informed consent form.

Exclusion Criteria:

1. Patients with the history of oral fluorouracil chemotherapy or Chinese medicine treatment;

2. Patients with organ dysfunction:

1. Renal function: serum creatinine>1.5 times the upper limit of normal

2. Liver function: total bilirubin>1.5 times the upper limit of normal,AST>1.5 times the upper limit of normal, alanine aminotransferase(ALT)>1.5 times the upper limit of normal or alkaline phosphatase (ALP) >2.5 times the upper limit of normal

3. Cardiac function:LVEF<50%;

3. Human epidermal growth factor receptor-2(HER-2) positive patients who cannot receive Herceptin treatment with a left ventricular ejection fraction(LVEF) less than 55%;

4. Patients allergic to docetaxel, capecitabine, epirubicin and cyclophosphamide;

5. Patients with severe systemic disease and/or uncontrollable infections;

6. Patients with previous malignancies, including contralateral breast cancer;

7. Patients with severe cardiovascular and cerebrovascular disease(i.e. Unstable angina, chronic cardiac failure, uncontrollable high blood pressure of >150/90 mmhg, myocardial infarction and cerebrovascular accident) history within 6 months before randomization;

8. Pregnant or lactating women.

9. Patients who have cognitive or psychological impairment as well as cannot understand the test program or stand side effects, which will result in a suspension of the trial program and follow-up;

10. Patients without personal freedom or independent civil capacity.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasm Female
• Breast Neoplasms

Intervention

Procedure:
• Neo-adjuvant Chemotherapy
A preoperative chemotherapy based on anthracyclines and taxanes.

Drug:
• Capecitabine
Capecitabine 1000mg/m2 tablets twice a day for 8 cycles.

Locations

Country	Name	City	State
China	the First Hospital of Jilin University	Changchun	Jilin

Sponsors (6)

Lead Sponsor	Collaborator
First Hospital of Jilin University	Baotou Cancer Hospital, First Affiliated Hospital Xi'an Jiaotong University, First Hospital of China Medical University, Qingdao University, The Second Affiliated Hospital of Harbin Medical University

Country where clinical trial is conducted

China, 

References & Publications (8)

Alliot C. In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer. Ann Oncol. 2005 Sep;16(9):1559-60; author reply 1560-1. — View Citation

Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclop — View Citation

Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. Effect of preoperative chemotherapy on local-regional disease in women with operable breast canc — View Citation

Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, — View Citation

M Toi, S-J Lee.Abstract S1-07: A phase III trial of adjuvant capecitabine in breast cancer patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy (CREATE-X, JBCRG-04). American Association for Cancer Research 76(4

Mathew J, Asgeirsson KS, Cheung KL, Chan S, Dahda A, Robertson JF. Neoadjuvant chemotherapy for locally advanced breast cancer: a review of the literature and future directions. Eur J Surg Oncol. 2009 Feb;35(2):113-22. doi: 10.1016/j.ejso.2008.03.015. Rev — View Citation

Mieog JS, van de Velde CJ. Neoadjuvant chemotherapy for early breast cancer. Expert Opin Pharmacother. 2009 Jun;10(9):1423-34. doi: 10.1517/14656560903002105. Review. — View Citation

Specht J, Gralow JR. Neoadjuvant chemotherapy for locally advanced breast cancer. Semin Radiat Oncol. 2009 Oct;19(4):222-8. doi: 10.1016/j.semradonc.2009.05.001. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival(DFS)		5 years	Yes
Secondary	Overall survival(OS)		5 years	Yes