Neoadjuvant Dose-dense EC Followed by ABX With PD-1 for Triple Negative Breast Cancer Patients

Study Overview
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Brief Summary
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This study is to evaluate the efficacy and safety for dose-dense epirubicin hydrochloride with cyclophosphamide followed by nanoparticlealbumin-bound paclitaxel with PD-1 in neoadjuvant therapy for patients with triple-negative breast cancer, and to explore the predictive value of biological markers for the treatment.

Detailed Description
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This study is an open single arm study, which would undergo optimal two stage designs. 60 patients who are diagnosed with triple-negative breast cancer would have dose-dense epirubicin hydrochloride with cyclophosphamide followed by nanoparticlealbumin-bound paclitaxel with PD-1 regimen for neoadjuvant therapy if they meet the eligibility criteria. The regimen is as follows: epirubicin hydrochloride (90mg/m2, d1) plus cyclophosphamide (600mg/m2, d1) every 14 days as one cycle for 4 cycles, followed by nanoparticlealbumin-bound paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles, and Toripalimab (240mg, d1) every 3 weeks as one cycle for 4 cycles. pathological complete response would be the primary endpoint. The change of biological markers and safety of the regimen would also be evaluated.

Official Title
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Dose-dense Epirubicin Hydrochloride With Cyclophosphamide Followed by Nanoparticlealbumin-bound Paclitaxel With PD-1 Regimen in Neoadjuvant Therapy for Patients With Triple-negative Breast Cancer

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: epirubicin hydrochloride
* Drug: Cyclophosphamide
* Drug: Albumin bound paclitaxel
* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female between 18 to 70 years old. Patients be diagnosed with primary unilateral invasive breast cancer of cT2-4NanyM0 by histology. Patients with ER negative and PR negative by immunohistochemistry (IHC), and HER-2 negative disease. HER2-negative disease was defined as follows: disease whose HER-2 is 1+ or negative by IHC, or fluorescence in situ hybridization (FISH) is negative if IHC is 2+. At least one mensurable objective focus according to RECIST guideline (vision 1.1). Eastern Cooperative Oncology Group (ECOG) performance status is less than or equal to (</=) 1. Baseline left ventricular ejection fraction (LVEF) is greater than or equal to (>/=) 55%. Bone marrow function is required as follows: neutrophils are more than or equal to (>/=) 1.5×109/L, platelets more than or equal to (>/=) 100×109/L, and hemoglobin more than or equal to (>/=) 90g/L. Hepatic and renal function are required as follows: serum creatinine is less than or equal to (</=) 1.5 times of upper limits of normal (ULN), aspartate transaminase (AST) and alanine aminotransferase (ALT) less than or equal to (</=) 2.5 times of ULN, and total bilirubin less than or equal to (</=) 1.5 times of ULN or </= 2.5 times of ULN if patient is with Gilbert's syndrome. Signed informed consent. Able to comply with the protocol. Exclusion Criteria: Received any previous therapy including cytotoxic chemotherapy, endocrine therapy, biological therapy or radiation therapy for any reason. Patients with heart disease whose New York Heart Association class (NYHA) is higher or equal to (>/=) Class II. Severe systemic infection or with other severe disease. Known hypersensitivity to any of the study drugs or excipients. Previous non-breast malignancy within 5 years prior to study entry excluding healed cervical carcinoma in situ and non-melanoma skin cancer. Pregnancy, breast-feeding or child-bearing women who refuse contraception during the trial. Participants who received any other investigational treatment within 30 days before the first dose of drug investigated. Patients who are inconformity to participate in this study according to investigators.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EC-ABX/PD-1<br>Patients who are treated with epirubicin hydrochloride andcyclophosphamide followed by nanoparticlealbumin-bound paclitaxel and Toripalimab | Drug: epirubicin hydrochloride<br>* Take epirubicin hydrochloride (90mg/m2, d1) every 14 days as one cycle for 4 cycles with cyclophosphamide, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.<br>Drug: Cyclophosphamide<br>* Take cyclophosphamide (600mg/m2, d1) every 14 days as one cycle for 4 cycles with epirubicin hydrochloride, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.<br>Drug: Albumin bound paclitaxel<br>* Take nanoparticlealbumin-bound paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles with Toripalimab, following epirubicin hydrochloride and cyclophosphamide.<br>Drug: Toripalimab<br>* Take Toripalimab (240mg, d1) every 3 weeks as one cycle for 4 cycles with nanoparticlealbumin-bound paclitaxel, following epirubicin hydrochloride and cyclophosphamide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response (pCR) | Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR. | Immediately after the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tumor-infiltrating lymphocytes (TILs) | TILs in tumor samples by biopsy right before the first neoadjuvant therapy (baseline) and by surgery immediately after surgery would be evaluated by HE or immune staining. TILs in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), right before and immediately after the surgery would also be obtained to evaluate its trends for the treatment. | before the first neoadjuvant chemotherapy (baseline), at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery | 
| Change in programmed cell death protein 1 (PD1) | PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment. | at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery | 
| Change in programmed cell death ligand 1 (PD-L1) | PD-L1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD-L1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment. | at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery | 
| Change in androgen receptor (AR) | AR in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. AR in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment. | at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery | 
| Change in cluster of differentiation 8 (CD8) | CD8 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. CD8 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment. | at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery | 
| Change in recombinant forkhead box protein C1 (FOXC1) | FOXC1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. FOXC1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment. | at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery | 
| Objective response rate (ORR) | Defined as the percentage of cases obtaining complete remission and partial response in all evaluable cases. | Immediately after the surgery | 
| Rate of breast-conserving surgery | Defined as the percentage of patients who have breast-conserving surgery in all evaluable patients. | Immediately after the surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Death-1