Carboplatin Intensified Chemotherapy for TRIple NEgative Breast Cancer(CITRINE)

Study Overview
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Brief Summary
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This is a prospective, single center, randomized, open-labled stage III clinical trial comparing the efficacy and safety of anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel combined with carboplatin for high-risk, triple-negative early breast cancer.

Detailed Description
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This is a prospective, single center, randomized, open-labled stage III clinical trial comparing the efficacy and safety of anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel combined with carboplatin for high-risk, triple-negative early breast cancer.High risk is defined as positive lymph nodes or negative lymph nodes but ki-67 is not less than 50%. We aim to explore whether the addition of carboplatin can improve the disease-free survival of early high-risk triple-negative breast cancer. At the same time, the experimental group's anthracyclines must be given in a dose-dense manner, while anthracyclines in the control group are dose-dense or not.

Official Title
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A Prospective, Single Center, Randomized, Open-labled Stage III Clinical Trial Comparing the Efficacy and Safety of Anthracyclin Followed by Weekly Paclitaxel Versus Dose-dense Anthracyclin Followed by Weekly Paclitaxel Versus Dose-dense Anthracyclin Followed by Weekly Paclitaxel Combined With Carboplatin for High-risk, Triple-negative Early Breast Cancer

Conditions
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Triple-negative Breast Cancer

Intervention / Treatment
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* Drug: Epirubicin
* Drug: CTX
* Drug: Paclitaxel
* Drug: ddEpirubicin
* Drug: ddCTX
* Drug: Paclitaxel(with carbo)
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Histologically documented TNBC after early breast cancer surgery (absence of HER2, ER, and PR expression) 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 ≥ 75 * 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). Women aged 18-70 years old; Lymph nodes positive or lymph nodes negative but with ki67 no less than 50% Have the cognitive ability to understand the protocol and be willing to participate and to be followed up For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm 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 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: conventional group<br>epirubincin 90mg/m2 d1 and CTX 600mg/m2 d1, every 2 or 3 weeks followed by paclitaxel 80mg/m2 d1,d8,d15, every 3 weeks. | Drug: Epirubicin<br>* 90mg/m2, d1 every 2 or 3 weeks<br>Drug: CTX<br>* 600mg, d1 every 2 or 3 weeks<br>Drug: Paclitaxel<br>* 80mg/m2,d1,d8,d15, every 3 weeks<br>|
| Experimental: carboplatin group<br>epirubincin 90mg/m2 d1 and CTX 600mg/m2 d1, every 2 weeks followed by paclitaxel 80mg/m2 and carboplatin AUC=2 d1,d8,d15, every 4 weeks. | Drug: ddEpirubicin<br>* 90mg/m2, d1 every 2 weeks<br>Drug: ddCTX<br>* 600mg, d1 every 2 weeks<br>Drug: Paclitaxel(with carbo)<br>* 80mg/m2,d1,d8,d15, every 4 weeks<br>Drug: Carboplatin<br>* AUC=2,d1,d8,d15, every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 3 year | 
| distant disease free survival |  | 3 year | 
| recurrence free survival |  | 3 year | 
| Disease free survival |  | 5 year | 
| overall survival |  | 5 year | 
| recurrence free survival |  | 5 year | 
| distant disease free survival |  | 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dose-dense chemotherapy, High-risk, Triple-negative Early Breast Cancer, Carboplatin