Clinical trial NCT04296175: Carboplatin Intensified Chemotherapy for TRIple NEgative Breast Cancer(CITRINE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Triple-negative Breast Cancer
Keywords: dose-dense chemotherapy
Carboplatin
High-risk, Triple-negative Early Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-03-05
Enrollment: 808
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomized controlled trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
2. Histologically documented TNBC after early breast cancer surgery (absence of HER2, ER, and PR expression)
3. 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).
4. Women aged 18-70 years old;
5. Lymph nodes positive or lymph nodes negative but with ki67 no less than 50%
6. Have the cognitive ability to understand the protocol and be willing to participate and to be followed up
7. 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:

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 breast cancer
5. Is pregnant, is breast feeding women, or women of childbearing age who cannot practice effective contraceptives;
6. Patients participating in other clinical trials at the same time;
7. 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;
8. Has known allergy to taxane
9. Has severe or uncontrolled infection;
10. Has a history of psychotropic substance abuse and were unable to abandon drug habits, or those with history of mental disorders;
11. the researchers judged patients to be unsuitable for the study.

Primary outcomes:
measure: Disease free survival
timeFrame: 3 year
Secondary outcomes:
measure: overall survival
timeFrame: 3 year
measure: distant disease free survival
timeFrame: 3 year
measure: recurrence free survival
timeFrame: 3 year
measure: Disease free survival
timeFrame: 5 year
measure: overall survival
timeFrame: 5 year
measure: recurrence free survival
timeFrame: 5 year
measure: distant disease free survival
timeFrame: 5 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhimin Shao, Professor
role: PRINCIPAL_INVESTIGATOR
References: