Clinical trial NCT03011060: Sequential Neo-adjuvant Chemotherapy Followed by Capecitabine Vs. Conventional Adjuvant Chemotherapy in Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Neoplasm Female
Keywords: neo-adjuvant chemotherapy
pathological complete response
Neoadjuvant Therapy
Capecitabine
Chemotherapy, Adjuvant
Lead sponsor: The First Hospital of Jilin University
Sponsor class: OTHER
Collaborators: name: First Hospital of China Medical University
name: The Second Affiliated Hospital of Harbin Medical University
name: Qingdao University
name: First Affiliated Hospital Xi'an Jiaotong University
name: Baotou Cancer Hospital
First posted: 2017-01-05
Enrollment: 1588
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

1. Pathologically confirmed unilateral invasive carcinoma (all pathological types);
2. No gross or microscopic residual tumor after resection;
3. Clinical stage Ⅰ-stage Ⅲ 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.

Primary outcomes:
measure: Disease-free survival(DFS)
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival(OS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Changchun
country: China
facility: the First Hospital of Jilin University
state: Jilin
Study officials:
affiliation: The First Hospital of Jilin University
name: Fan Zhimin, Professor
role: STUDY_CHAIR
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