Clinical trial NCT03926091: Study Comparing 4 Cycles With 6 Cycles of TC (Docetaxel+Cyclophosphamide) Adjuvant Chemotherapy for 1-3 Lymph Node Positive ER+/HER2- Early Breast Cancer
Official title: A Prospective, Multisite, Randomized, Open-label Phase III Clinical Trial (CLOVER Study)Comparing 4 Cycles With 6 Cycles of TC (Docetaxel+Cyclophosphamide) Adjuvant Chemotherapy for 1-3 Lymph Node Positive ER+/HER2- Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: docetaxel
cyclophosphamide
adjuvant chemotherapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2019-04-24
Enrollment: 2172
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1：6 cycles of TC (Docetaxel 75 mg/m\^2 ivgtt d1+Cyclophosphamide 600 mg/m\^2 iv d1, 21 days per cycle).

Arm 2：4 cycles of TC (Docetaxel 75 mg/m\^2 ivgtt d1+Cyclophosphamide 600 mg/m\^2 iv d1, 21 days per cycle).
Primary purpose: TREATMENT

Brief summary: This is a prospective, multisite, randomized, open-label Phase III clinical trial (CLOVER study) comparing 4 cycles with 6 cycles of TC (docetaxel+cyclophosphamide) adjuvant chemotherapy for 1-3 positive lymph node, ER+/HER2- early breast cancer patients.

Detailed description: While TC (docetaxel+cyclophosphamide) adjuvant chemotherapy is one of the preferred regimens for early breast cancer, we have yet to determine the optimum number of cycles for TC adjuvant chemotherapy. In this prospective, open-label clinical trial, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients with 1-3 positive lymph nodes will be randomized into either 4 cycles or 6 cycles of TC adjuvant chemotherapy. The safety and efficacy of each group will be assessed through disease-free survival (DFS), invasive disease free survival (iDFS), distant disease free survival (DDFS), overall survival (OS) and adverse effects (AE) as graded by Common Terminology Criteria for Adverse Events (CTCAE) 4.0.

Eligibility criteria: Inclusion Criteria:

1. women aged 18-70 years old;
2. Patient has localized invasive breast carcinoma with1-3 positive lymph nodes, and is ER+/HER2- confirmed by histopathology after early breast cancer surgery（HER2-negative breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescence in situ hybridization (FISH), Chromogenic in situ hybridization (CISH) , or Silver in situ hybridization (SISH)) test is required by local laboratory testing.), with at least one of the following conditions: (1) histological grade III; (2) Ki67 ≥ 30%; (3) progesterone receptor (PR) ≤ 20% positive; (4) age less than 35 years; (5) extensive vascular tumor thrombus; (6) multigene detection recurrence score (RS) \>25;
3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
4. Has adequate organ function meeting the following criteria: (1) adequate bone marrow function: hemoglobin ≥ 90 g/L (no blood transfusion within 14 days); absolute neutrophil count ≥ 1.5 x 109 /L; platelet count ≥ 100 \* 109 /L; (2)adequate liver and kidney function: Alanine Aminotransferase (ALT) ≤ 3×upper limit of normal (ULN), Aspartate Aminotransferase (AST) ≤ 3×ULN, Total Bilirubin (TBIL)≤ 1.5×ULN, serum creatinine ≤ 1×ULN，and with endogenous creatinine clearance rate of \>50 ml/min (Cockcroft-Gault formula).
5. Participants voluntarily joined the study, has signed informed consent before any trial related activities are conducted, has good compliance and has agreed to follow-up.

Exclusion Criteria:

1. Has received neoadjuvant therapy (include chemotherapy, targeted therapy, radiotherapy or endocrine therapy）;
2. Has bilateral breast cancer;
3. Has previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ.
4. Has metastatic (Stage 4) breast cancer;
5. Has any \>T4 lesion (UICC1987) (with skin involvement, mass adhesion and fixation, and inflammatory breast cancer);
6. Is pregnant, is breast feeding women, or women of childbearing age who cannot practice effective contraceptives;
7. Patients participating in other clinical trials at the same time;
8. Has severe organ dysfunction (cardiopulmonary liver and kidney) insufficiency, left ventricular ejection fraction (LVEF) \< 50% (cardiac ultrasound); severe cardio cerebral vascular disease within the 6 months previous of randomization (such as unstable angina, chronic heart failure, uncontrolled hypertension with blood pressure\>150/90mmgh, myocardial infarction, or cerebral blood vessel); diabetic patients with poor blood glucose control; patients with severe hypertension;
9. Has known allergy to taxane and excipients.
10. Has severe or uncontrolled infection;
11. Has a history of psychotropic substance abuse and were unable to abandon drug habits, or those with history of mental disorders;
12. the researchers judged patients to be unsuitable for the study.

Primary outcomes:
measure: Invasive disease free survival
timeFrame: 5 year
Secondary outcomes:
measure: disease free survival
timeFrame: 5 years
measure: distant disease free survival
timeFrame: 5 years
measure: overall survival
timeFrame: 5 years
measure: adverse effects
timeFrame: 5 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yet-Sen Memorial Hospital, Sun Yet-Sen University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University (The First Hospital of Jilin University)
state: Jilin
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: OB/GYN Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Hospital
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, ZheJiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Hanzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Zhimin Shao, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: