Breast CancerPhase 3CLOVERNCT03926091
Study Comparing 4 Cycles With 6 Cycles of TC (Docetaxel+Cyclophosphamide) Adjuvant Chemotherapy for 1-3 Lymph Node Positive ER+/HER2- Early Breast Cancer
A Phase 3 study testing Docetaxel and Cyclophosphamide in people with Breast Cancer, run by Fudan University at 14 sites in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Docetaxel and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,172 participants
- Where
- 14 sitesChina
- Study dates
- 1 Apr 2019to 1 Nov 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 12Show fewer
- 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.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
China14 sites, 14 recruiting
- Recruiting
The First Bethune Hospital of Jilin University (The First Hospital of Jilin University)
Changchun, Jilin, 130021
Zhimin Fan, M.D., +86-431-88782222
- Recruiting
Chongqing Cancer Hospital
Chongqing, Chongqing Municipality, 400030
Xiaohua Zeng, M.D., +86-023-65311341
- Recruiting
The Second Hospital of Dalian Medical University
Dalian, Liaoning, 116027
Man Li, M.D., +86-411-84671291
- Recruiting
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001
Chuangui Song, M.D,, +86-591-83357896
- Recruiting
Sun Yet-Sen Memorial Hospital, Sun Yet-Sen University
Guangzhou, Guangdong, 510120
Qiang Liu, M.D., +86-020-81332199
- Recruiting
The First Affiliated Hospital, ZheJiang University
Hangzhou, Zhejiang, 310003
Peifen Fu, M.D., zdyy6616@126.com
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Hongjian Yang, M.D., +86-571-88122222, zjszlyy@zjcc.org.cn
- Recruiting
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hanzhou, Zhejiang, 310009
Jian Huang, M.D., +86-571-87783777
- Recruiting
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081
Zhigao Li, M.D., +86-451-86298000
- Recruiting
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266000
Haibo Wang, M.D.
- Recruiting
OB/GYN Hospital of Fudan University
Shanghai, Shanghai Municipality, 200011
Kejin Wu, M.D., +86-021-33189900
- Recruiting
Fudan University Shanghai Cancer Hospital
Shanghai, Shanghai Municipality, 200032
Zhimin Shao, M.D., +86-021-64175590 ext. 8808, zhimingshao@yahoo.com
- Recruiting
The First Hospital of China Medical University
Shenyang, Liaoning, 110001
Feng Jin, M.D., +86-024-83283333
- Recruiting
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300052
Jin Zhang, M.D.
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Docetaxel, Cyclophosphamide
- Keywords
- docetaxel, cyclophosphamide, adjuvant chemotherapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Also called docetaxel injection
Docetaxel chemotherapy (injection)
CyclophosphamideDrug
Also called Cyclophosphamide injection
Cyclophosphamide chemotherapy (injection)
| Study group | Role | What they receive |
|---|---|---|
| 4 cycles of TC adjuvant chemotherapy | Experimental | 4 cycles of TC (Docetaxel 75 mg/m^2 ivgtt d1+Cyclophosphamide 600 mg/m^2 iv d1, 21 days per cycle). Receives: Drug: Docetaxel; Drug: Cyclophosphamide |
| 6 cycles of TC adjuvant chemotherapy | Active comparator | 6 cycles of TC (Docetaxel 75 mg/m^2 ivgtt d1+Cyclophosphamide 600 mg/m^2 iv d1, 21 days per cycle). Receives: Drug: Docetaxel; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive disease free survival
Measured: 5 year
Secondary outcomes (4)
disease free survival
Measured: 5 years
distant disease free survival
Measured: 5 years
overall survival
Measured: 5 years
adverse effects
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2019
- Study start1 Apr 2019
- Primary completion1 Nov 2024 (estimated)
- Study completion1 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 2,172 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhimin Shao, Fudan University
- Investigators
- Zhimin Shao, MD, PhD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03926091
- Sponsor's protocol ID
- CLOVER
- Acronym
- CLOVER
- Status last verified
- Nov 2023
- First submitted
- 31 Mar 2019
- Last updated
- 14 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03926091
- Acronym / sponsor ID
- CLOVER / CLOVER
- Conditions
- Breast Cancer
- Keywords
- docetaxel, cyclophosphamide, adjuvant chemotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,172 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 1 Nov 2024 (estimated)
- Study completion
- 1 Nov 2025 (estimated)
- First posted
- 24 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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 | Type | Receives |
|---|---|---|
| 4 cycles of TC adjuvant chemotherapy | Experimental | Drug: Docetaxel, Drug: Cyclophosphamide4 cycles of TC (Docetaxel 75 mg/m^2 ivgtt d1+Cyclophosphamide 600 mg/m^2 iv d1, 21 days per cycle). |
| 6 cycles of TC adjuvant chemotherapy | Active comparator | Drug: Docetaxel, Drug: Cyclophosphamide6 cycles of TC (Docetaxel 75 mg/m^2 ivgtt d1+Cyclophosphamide 600 mg/m^2 iv d1, 21 days per cycle). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DocetaxelAlso: docetaxel injectionDocetaxel chemotherapy (injection) | Drug | 4 cycles of TC adjuvant chemotherapy, 6 cycles of TC adjuvant chemotherapy |
| CyclophosphamideAlso: Cyclophosphamide injectionCyclophosphamide chemotherapy (injection) | Drug | 4 cycles of TC adjuvant chemotherapy, 6 cycles of TC adjuvant chemotherapy |
Primary outcome
Invasive disease free survival
Time frame: 5 year
4 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2023.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhimin Shao, MD, PhD principal investigator
Fudan University
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Docetaxel and Cyclophosphamide in people with Breast Cancer, run by Fudan University at 14 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhimin Shao, MD, PhD (+86-021-64175590 ext. 8808, zhimingshao@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Invasive disease free survival (time frame: 5 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2023.