Carboplatin Intensified Chemotherapy for TRIple NEgative Breast Cancer(CITRINE) (CITRINE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Triple-negative Breast Cancer
• Intervention / Treatment: Drug: Epirubicin; Drug: CTX; Drug: Paclitaxel; Drug: ddEpirubicin; Drug: ddCTX; Drug: Paclitaxel(with carbo); Drug: Carboplatin

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.

• Study Type: Interventional
• Enrollment (Estimated): 808
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhimin Shao, Professor; Phone Number: 88807 08664175590; Email: zhimingshao@yahoo.com
• Study Contact Backup: Name: Zhonghua Wang, Professor; Phone Number: 88603 08664175590; Email: zhonghuawang95@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Zhimin Shao, M.D.; Phone Number: 88807 08664175590; Email: zhimingshao@yahoo.com
      • Contact: Yin Liu, M.D.; Phone Number: 88603 08664175590; Email: liuyinfudan@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: conventional group; 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; 90mg/m2, d1 every 2 or 3 weeks; Drug: CTX; 600mg, d1 every 2 or 3 weeks; Drug: Paclitaxel; 80mg/m2,d1,d8,d15, every 3 weeks
Experimental: carboplatin group; 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; 90mg/m2, d1 every 2 weeks; Drug: ddCTX; 600mg, d1 every 2 weeks; Drug: Paclitaxel(with carbo); 80mg/m2,d1,d8,d15, every 4 weeks; Drug: Carboplatin; AUC=2,d1,d8,d15, every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	3 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhimin Shao, Professor, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 3, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Carboplatin; dose-dense chemotherapy; High-risk, Triple-negative Early Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Carboplatin; Paclitaxel; Epirubicin; Albumin-Bound Paclitaxel
• Other Study ID Numbers: 1807187-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No