Comparing 4 vs 6 cycles of chemotherapy for early breast cancer

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

This study is testing whether women with early breast cancer do better with 4 or 6 cycles of chemotherapy to see which option is more effective and safer.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 2172 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Fudan University (other)
• Drugs / interventions: chemotherapy, cyclophosphamide
• Locations: 14 sites (Chongqing, Chongqing and 13 other locations)
• Trial ID: NCT03926091 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of 4 cycles versus 6 cycles of adjuvant chemotherapy using docetaxel and cyclophosphamide in women with early breast cancer that has 1-3 positive lymph nodes and is ER+/HER2-. Participants will be randomly assigned to one of the two treatment groups, and the study will assess various outcomes including disease-free survival and overall survival, as well as the safety profile of each regimen. The trial aims to determine the optimal number of chemotherapy cycles needed for effective treatment.

Who should consider this trial

Good fit: Ideal candidates are women aged 18-70 with localized invasive ER+/HER2- breast cancer and 1-3 positive lymph nodes.

Not a fit: Patients with HER2-positive breast cancer or those who do not meet the specific eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help optimize chemotherapy treatment regimens for early breast cancer patients, potentially improving survival rates and reducing unnecessary treatment exposure.

How similar studies have performed: Previous studies have shown varying success with different chemotherapy regimens, but this specific comparison of cycle numbers is novel.

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.

Where this trial is running

Chongqing, Chongqing and 13 other locations

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

Study contacts

• Principal investigator: Zhimin Shao, MD, PhD — Fudan University
• Study coordinator: Zhimin Shao, MD, PhD

Conditions: Breast Cancer, docetaxel, cyclophosphamide, adjuvant chemotherapy