Study Comparing 4 Cycles With 6 Cycles of TC (Docetaxel+Cyclophosphamide) Adjuvant Chemotherapy for 1-3 Lymph Node Positive ER+/HER2- Early Breast Cancer

Breast Cancer Clinical Trial

— CLOVER  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03926091
• Other study ID #: CLOVER
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2019
• Est. completion date: November 1, 2025

Study information

• Verified date: November 2023
• Source: Fudan University
• Contact: Zhimin Shao, MD, PhD
• Phone: +86-021-64175590
• Email: zhimingshao[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2172
• Est. completion date: November 1, 2025
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Docetaxel
Docetaxel chemotherapy (injection)
• Cyclophosphamide
Cyclophosphamide chemotherapy (injection)

Locations

Country	Name	City	State
China	The First Bethune Hospital of Jilin University (The First Hospital of Jilin University)	Changchun	Jilin
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	The Second Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun Yet-Sen Memorial Hospital, Sun Yet-Sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital, ZheJiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hanzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Fudan University Shanghai Cancer Hospital	Shanghai	Shanghai
China	OB/GYN Hospital of Fudan University	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive disease free survival		5 year
Secondary	disease free survival		5 years
Secondary	distant disease free survival		5 years
Secondary	overall survival		5 years
Secondary	adverse effects		5 years