Adjuvant Chemotherapy for Triple Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of antharcycline-based adjuvant chemotherapy compared with observation in triple negative breast cancer (TNBC) patients with residual invasive disease after platinum and taxanes based neoadjuvant chemotherapy.

Detailed Description
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This study is a multi-center, randomized, phase II study. TNBC patients with residual invasive disease (invasive breast tumor size≥1cm and/or positive axillary lymph nodes) after platinum and taxanes based neoadjuvant chemotherapy are enrolled (n = 286). Patients are assigned to the chemotherapy group or the observation group at a 1:1 ratio randomly 4-6 weeks after surgery. Patients in the chemotherapy group are given anthracycline combined with cyclophosphamide regimen for 4 cycles. At the same time, the blood and tissue samples are collected for relevant tests. Follow up every 3-6 months and record recurrences and deaths.

Official Title
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A Multicenter, Randomised, Open-label Phase II Study to Evaluate the Efficacy and Safety of Adjuvant Chemotherapy for Triple Negative Breast Cancer Patients With Residual Disease After Platinum-based Neoadjuvant Chemotherapy

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Epirubicin or Pirarubicin
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed invasive adenocarcinoma of the breast. Triple negative breast cancer: hormone receptor negative (ER < 10% and PgR < 10%) and HER2 negative (IHC 0/1+ or ISH non-amplified), as defined by the local pathology laboratory. Clinical stage at presentation: T1-4, N0-3, M0, with indications for neoadjuvant chemotherapy. Patient must have received platinum and taxanes neoadjuvant chemotherapy for at least 4 cycles and no tumor progression occurred. Patients should have undergone adequate tumor excision in the breast and lymph nodes after neoadjuvant chemotherapy. Residual invasive disease must be ≥1cm in the breast, and/or have positive axillary lymph nodes observed on pathologic exam after neoadjuvant chemotherapy. ECOG Performance Status: 0-1. Patients without severe heart, lung, liver and kidney disease. Adequate hematologic and end-organ function. No more than 6 weeks may elapse between definitive breast surgery and randomization. Exclusion Criteria: Previous neoadjuvant chemotherapy with anthracycline or other drugs (except platinum and taxanes). Previous neoadjuvant chemotherapy with platinum or taxanes alone. Patients have received other adjuvant therapy. Comprehensive medical examinations have revealed distant metastases before randomization. Patients who are not suitable for anthracycline evaluated by investigators. Prior history of other malignancy (except carcinoma in situ).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: Adjuvant chemotherapy<br>Adjuvant chemotherapy for triple negative breast cancer with residual invasive disease (invasive breast tumor size≥1cm and/or positive axillary lymph nodes) after taxanes and platinum based neoadjuvant chemotherapy. Adjuvant chemotherapy regiments: Epirubicin 80-90mg/m2 IV or Pirarubicin 50mg/m2 IV + Cyclophosphamide 600mg/m2 IV, q21d*4cycles. | Drug: Epirubicin or Pirarubicin<br>* Epirubicin 80-90mg/m2 IV or Pirarubicin 50mg/m2 IV, q21d*4cycls<br>* Other names: EPI or THP;Drug: Cyclophosphamide<br>* Cyclophosphamide 600mg/m2 IV, q21d*4cycls<br>* Other names: CTX;|
| No Intervention: Observation<br>No adjuvant chemotherapy for triple negative breast cancer with residual invasive disease (invasive breast tumor size≥1cm and/or positive axillary lymph nodes) after taxanes and platinum based neoadjuvant chemotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RFS | RFS defined as the time from randomization to the first recurrence event or death through the end of study | median 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | OS defined as the time from randomization to all-cause death through the end of study | median 5 years | 
| Percentage of patients with adverse events | To assess the toxicity of adjuvant chemotherapy by CTCAE v5.0 | 2-3 years | 
| Changes in patient-reported quality of life | To assess the mean changes from baseline score in patient-reported quality of life using EORTC QLQ-C30 | 2-3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Triple negative breast cancer, Neoadjuvant chemotherapy, Residual invasive breast cancer, Adjuvant chemotherapy