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

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03926091

Collaborator

(none)

2,172

Enrollment

Locations

Arms

Anticipated Duration (Months)

155.1

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Docetaxel Drug: Cyclophosphamide	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2172 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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).Arm 1：6 cycles of TC (Docetaxel 75 mg/m2 ivgtt d1+Cyclophosphamide 600 mg/m2 iv d1, 21 days per cycle). Arm 2：4 cycles of TC (Docetaxel 75 mg/m2 ivgtt d1+Cyclophosphamide 600 mg/m2 iv d1, 21 days per cycle).

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 3, 2018

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4 cycles of TC adjuvant chemotherapy 4 cycles of TC (Docetaxel 75 mg/m^2 ivgtt d1+Cyclophosphamide 600 mg/m^2 iv d1, 21 days per cycle).	Drug: Docetaxel Docetaxel chemotherapy (injection) Drug: Cyclophosphamide Cyclophosphamide chemotherapy (injection)
Active Comparator: 6 cycles of TC adjuvant chemotherapy 6 cycles of TC (Docetaxel 75 mg/m^2 ivgtt d1+Cyclophosphamide 600 mg/m^2 iv d1, 21 days per cycle).	Drug: Docetaxel Docetaxel chemotherapy (injection) Drug: Cyclophosphamide Cyclophosphamide chemotherapy (injection)

Arm

Intervention/Treatment

Experimental: 4 cycles of TC adjuvant chemotherapy

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

Drug: Docetaxel

Docetaxel chemotherapy (injection)

Drug: Cyclophosphamide

Cyclophosphamide chemotherapy (injection)

Active Comparator: 6 cycles of TC adjuvant chemotherapy

6 cycles of TC (Docetaxel 75 mg/m^2 ivgtt d1+Cyclophosphamide 600 mg/m^2 iv d1, 21 days per cycle).

Drug: Docetaxel

Docetaxel chemotherapy (injection)

Drug: Cyclophosphamide

Cyclophosphamide chemotherapy (injection)

Outcome Measures

Primary Outcome Measures

Disease free survival [5 year]

Secondary Outcome Measures

invasive disease free survival [5 years]
distant disease free survival [5 years]
overall survival [5 years]
adverse effects [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

women aged 18-70 years old;
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;
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
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).
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:

Has received neoadjuvant therapy (include chemotherapy, targeted therapy, radiotherapy or endocrine therapy）;
Has bilateral breast cancer;
Has previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ.
Has metastatic (Stage 4) breast cancer;
Has any >T4 lesion (UICC1987) (with skin involvement, mass adhesion and fixation, and inflammatory breast cancer);
Is pregnant, is breast feeding women, or women of childbearing age who cannot practice effective contraceptives;
Patients participating in other clinical trials at the same time;
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;
Has known allergy to taxane and excipients.
Has severe or uncontrolled infection;
Has a history of psychotropic substance abuse and were unable to abandon drug habits, or those with history of mental disorders;
the researchers judged patients to be unsuitable for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chongqing Cancer Hospital	Chongqing	Chongqing	China	400030
2	Fujian Medical University Union Hospital	Fuzhou	Fujian	China	350001
3	Sun Yet-Sen Memorial Hospital, Sun Yet-Sen University	Guangzhou	Guangdong	China	510120
4	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150081
5	The First Bethune Hospital of Jilin University (The First Hospital of Jilin University)	Changchun	Jilin	China	130021
6	The Second Hospital of Dalian Medical University	Dalian	Liaoning	China	116027
7	The First Hospital of China Medical University	Shenyang	Liaoning	China	110001
8	The Affiliated Hospital of Qingdao University	Qingdao	Shandong	China	266000
9	OB/GYN Hospital of Fudan University	Shanghai	Shanghai	China	200011
10	Fudan University Shanghai Cancer Hospital	Shanghai	Shanghai	China	200032
11	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin	China	300052
12	The First Affiliated Hospital, ZheJiang University	Hangzhou	Zhejiang	China	310003
13	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310022
14	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hanzhou	Zhejiang	China	310009