Evaluation of Sequencing of Anthracyclines and Taxanes for Locally Advanced HER2-negative Breast Cancer

Study Overview
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Brief Summary
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Phase III randomized clinical trial evaluating the sequencing of anthracyclines and taxanes in neoadjuvant therapy for locally advanced HER2-negative breast cancer.

Detailed Description
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Multicenter, phase III, open-label, randomized clinical trial, which will include 494 patients randomized to two neoadjuvant chemotherapy arms. The treatment protocol will be the same in both groups, only the regimens sequences will be evaluated: starting with anthracycline versus taxane, with or without carboplatin for patients with triple negative subtype. The chemotherapy regimen will follow the institution's routine, which includes the use of CA in the anthracyclical phase and, in the taxane phase, the use of docetaxel every 21 days or weekly paclitaxel. The rest of the treatment (surgery, radiotherapy, hormone therapy) will not be part of the study and will be carried out according to institutional guidelines.

Official Title
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Phase III Randomized Clinical Trial Evaluating the Sequencing of Anthracyclines and Taxanes in Neoadjuvant Therapy for Locally Advanced HER2-negative Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel or Paclitaxel
* Drug: Cyclophosphamide + Doxorrubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants, with at least 18 years old on the day of signing the free and informed consent; Invasive breast carcinoma stage III (RH positive) or IIB/III (RH negative), according to TNM 8th edition; Histologically confirmed diagnosis of invasive breast carcinoma (with any histology), HER-2 negative; The participant (or legally acceptable representative, if applicable) provides written informed consent for the study; The participant must agree to use a contraceptive as detailed in Appendix B of this protocol during the treatment period and for at least 120 days after the last dose of the study treatment; Have a functional capacity according to the Eastern Cooperative Oncology Group (ECOG) from 0 to 2. The evaluation of the ECOG must be carried out within 7 days before the inclusion date. Have adequate organic function. The samples must be collected within 60 days before the start of the study treatment; Have adequate cardiac function as assessed by echocardiogram or MUGA performed up to 60 days before the start of treatment under study. Exclusion Criteria: - Individuals who do not meet the inclusion criteria above-mentioned.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Start with Cyclophosphamide + Doxorrubicin<br>Patients will receive the following treatment schedule: Doxorubicin 60mg/m²; Cyclophosphamide 600mg/m² intravenously every 21 days for 3 cycles, followed by docetaxel 75-100mg/m2 intravenously every 21 days for 4 cycles or weekly paclitaxel 80mg/m2 for 12 weeks. | Drug: Cyclophosphamide + Doxorrubicin<br>* Treatment will start with Doxorubicin 60mg/m²; Cyclophosphamide 600mg/m² intravenously every 21 days for 3 cycles<br>* Other names: Citoxan + Rubidox;|
| Experimental: Start with Docetaxel or Paclitaxel<br>Patients will receive the following treatment schedule: Docetaxel 75-100mg/m² intravenously every 21 days for 4 cycles or weekly paclitaxel 80mg/m² for 12 weeks, followed by Doxorubicin 60mg/m²; Cyclophosphamide 600mg/m² intravenously every 21 days, for 3 cycles. | Drug: Docetaxel or Paclitaxel<br>* Treatment will start with Docetaxel 75-100mg/m² intravenously every 21 days for 4 cycles or weekly paclitaxel 80mg/m² for 12 weeks<br>* Other names: Taxotere or Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive disease-free survival (IDFS) | Defined as the time elapsed between the date of randomization and the date of invasive recurrence (excludes carcinoma in situ) or death, whichever comes first.. | An average of 8 years |