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

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
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Study Type : Interventional  (Clinical Trial)
Estimated 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).

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 : July 3, 2018
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2024
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)

Outcome Measures
Primary Outcome Measures :
  1. Disease free survival [ Time Frame: 5 year ]

Secondary Outcome Measures :
  1. invasive disease free survival [ Time Frame: 5 years ]
  2. distant disease free survival [ Time Frame: 5 years ]
  3. overall survival [ Time Frame: 5 years ]
  4. adverse effects [ Time Frame: 5 years ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Contacts
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Contact: Zhimin Shao, MD, PhD +86-021-64175590 ext 8808 zhimingshao@yahoo.com

Locations
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China, Chongqing
Chongqing Cancer Hospital Recruiting
Chongqing, Chongqing, China, 400030
Contact: Xiaohua Zeng, M.D.    +86-023-65311341      
China, Fujian
Fujian Medical University Union Hospital Recruiting
Fuzhou, Fujian, China, 350001
Contact: Chuangui Song, M.D,    +86-591-83357896      
China, Guangdong
Sun Yet-Sen Memorial Hospital, Sun Yet-Sen University Recruiting
Guangzhou, Guangdong, China, 510120
Contact: Qiang Liu, M.D.    +86-020-81332199      
China, Heilongjiang
Harbin Medical University Cancer Hospital Recruiting
Harbin, Heilongjiang, China, 150081
Contact: Zhigao Li, M.D.    +86-451-86298000      
China, Jilin
The First Bethune Hospital of Jilin University (The First Hospital of Jilin University) Recruiting
Changchun, Jilin, China, 130021
Contact: Zhimin Fan, M.D.    +86-431-88782222      
China, Liaoning
The Second Hospital of Dalian Medical University Recruiting
Dalian, Liaoning, China, 116027
Contact: Man Li, M.D.    +86-411-84671291      
The First Hospital of China Medical University Recruiting
Shenyang, Liaoning, China, 110001
Contact: Feng Jin, M.D.    +86-024-83283333      
China, Shandong
The Affiliated Hospital of Qingdao University Recruiting
Qingdao, Shandong, China, 266000
Contact: Haibo Wang, M.D.         
China, Shanghai
OB/GYN Hospital of Fudan University Recruiting
Shanghai, Shanghai, China, 200011
Contact: Kejin Wu, M.D.    +86-021-33189900      
Fudan University Shanghai Cancer Hospital Recruiting
Shanghai, Shanghai, China, 200032
Contact: Zhimin Shao, M.D.    +86-021-64175590 ext 8808    zhimingshao@yahoo.com   
China, Tianjin
Tianjin Medical University Cancer Institute and Hospital Recruiting
Tianjin, Tianjin, China, 300052
Contact: Jin Zhang, M.D.         
China, Zhejiang
The First Affiliated Hospital, ZheJiang University Recruiting
Hangzhou, Zhejiang, China, 310003
Contact: Peifen Fu, M.D.       zdyy6616@126.com   
Zhejiang Cancer Hospital Recruiting
Hangzhou, Zhejiang, China, 310022
Contact: Hongjian Yang, M.D.    +86-571-88122222    zjszlyy@zjcc.org.cn   
The Second Affiliated Hospital of Zhejiang University School of Medicine Recruiting
Hanzhou, Zhejiang, China, 310009
Contact: Jian Huang, M.D.    +86-571-87783777      
Sponsors and Collaborators
Fudan University
Investigators
Layout table for investigator information
Principal Investigator: Zhimin Shao, MD, PhD Fudan University
Tracking Information
First Submitted Date  ICMJE March 31, 2019
First Posted Date  ICMJE April 24, 2019
Last Update Posted Date March 9, 2020
Actual Study Start Date  ICMJE July 3, 2018
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
Disease free survival [ Time Frame: 5 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • invasive disease free survival [ Time Frame: 5 years ]
  • distant disease free survival [ Time Frame: 5 years ]
  • overall survival [ Time Frame: 5 years ]
  • adverse effects [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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).

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Docetaxel
    Docetaxel chemotherapy (injection)
  • Drug: Cyclophosphamide
    Cyclophosphamide chemotherapy (injection)
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Docetaxel
    • Drug: Cyclophosphamide
  • 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).
    Interventions:
    • Drug: Docetaxel
    • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2019)
2172
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2024
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zhimin Shao, MD, PhD +86-021-64175590 ext 8808 zhimingshao@yahoo.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03926091
Other Study ID Numbers  ICMJE CLOVER
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Zhimin Shao, Fudan University
Study Sponsor  ICMJE Fudan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Zhimin Shao, MD, PhD Fudan University
PRS Account Fudan University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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