Mutation Scores and Differential Protein Evaluating Efficacy in Adjuvant Chemotherapy in HER2(-) Luminal B Breast Cancer

Study Overview
=================
Brief Summary
-----------------
We plan to carry out a prospective, randomized, open phase III clinical trial which sponsored by the Tianjin Medical University Cancer Hospital and Institute. The primary aim is to evaluate pCR of DT and ET regimen as neoadjuvant chemotherapy in the treatment of HER2 negative Luminal B breast cancers and the correlation of pCR respectively with the susceptible gene mutation scores and differential protein identified by proteomics. For patients with pCR, the association between the 5 year DFS and susceptible gene mutation scores and differential protein identified by proteomics will be evaluated. All Non-pCR patients will receive NX chemotherapy for 4 cycles, and to evaluate correlations between 5 year DFS of these patients respectively with susceptible gene mutation scores and differential protein identified by proteomics, and to evaluate the safety of neoadjuvant chemotherapy and sequential adjuvant NX regimen therapy. Meanwhile, we will verify susceptible gene mutation scores and differential protein identified by proteomics are significant predictors of HER2 negative Luminal B breast cancer chemotherapy sensitivity and prognosis, and explore the feasibility of susceptible gene mutation scores and differential protein in clinical application.

Detailed Description
-----------------
This is a prospective, randomized, open phase III clinical trial which will be sponsored by the Tianjin Medical University Cancer Hospital and Institute. The primary aim is to evaluate pCR of Pegylated Liposomal Doxorubicin and Docetaxel (DT) Compared to Conventional Doxorubicin and Docetaxel (ET) regimen as neoadjuvant chemotherapy in the treatment of HER2 negative Luminal B breast cancers and the correlation of pCR respectively with the susceptible gene mutation scores and differential protein identified by proteomics. For patients with pCR, the association between the 5 year DFS and susceptible gene mutation scores and differential protein identified by proteomics will be evaluated. All Non-pCR patients will receive NX chemotherapy for 4 cycles, and to evaluate correlations between 5 year DFS of these patients respectively with susceptible gene mutation scores and differential protein identified by proteomics, and to evaluate the safety of neoadjuvant chemotherapy and sequential adjuvant Nalvelbine and Xeloda (NX) regimen therapy. Meanwhile, we will verify susceptible gene mutation scores and differential protein identified by proteomics are significant predictors of HER2 negative Luminal B breast cancer chemotherapy sensitivity and prognosis, and explore the feasibility of susceptible gene mutation scores and differential protein in clinical application.

Official Title
-----------------
Mutation Scores and Differential Protein Evaluating Efficacy in Neo-adjuvant Chemotherapy and the Non-PCR Patients Treated With Sequential Nalvelbine and Xeloda in HER2(-) Luminal B Breast Cancer

Conditions
-----------------
Susceptibility, Genetic, Chemotherapy Effect

Intervention / Treatment
-----------------
* Drug: DT group
* Drug: ET group
* Drug: NX group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent form Compliance with test procedures and good compliance Females, Age more than 18 years of age, less than 70 years old The ECOG score is 0-1 Primary invasive cancer, T2-4bN0-2M0 breast cancers Neoadjuvant chemotherapy with standard 6 courses should be completed Patients must undergo standard breast cancer surgery after neoadjuvant chemotherapy Luminal B, Her2 negative patients No other malignant tumors occurred at the same time adequate liver and kidney function Exclusion Criteria: Any metastasis Suffered other maligant tumors Participate in other trials Accompanied with severe systemic disease and / or uncontrollable infection Pregnant and lactating women Dysfunction of liver and kidney

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DT group<br>Pegylated liposomal doxorubicin and Docetaxel Treatment group Pegylated liposomal doxorubicin 30mg/m2，iv，d1， Docetaxel 75mg/m2，iv，d1， q21d×6 | Drug: DT group<br>* Pegylated liposomal doxorubicin 30mg/m2，iv，d1， Docetaxel 75mg/m2，iv，d1， q21d×6<br>* Other names: Pegylated liposomal doxorubicin and Docetaxel;|
| Active Comparator: ET group<br>Conventional doxorubicin and Docetaxel Treatment group Conventional doxorubicin 75mg/m2，iv，d1， Docetaxel 75mg/m2，iv，d1， q21d×6 | Drug: ET group<br>* Conventional doxorubicin 75mg/m2，iv，d1， Docetaxel 75mg/m2，iv，d1， q21d×6<br>* Other names: Conventional doxorubicin and Docetaxel;|
| Experimental: NX group<br>Navelbine and Xeloda treatment group in group of Non-pCR patients Navelbine IVD 25 mg/m2 D1、D8 Xeloda PO 1000 mg/m2 bid D1-D14 q21d×4 | Drug: NX group<br>* Navelbine IVD 25 mg/m2 D1、D8 Xeloda PO 1000 mg/m2 bid D1-D14 q21d<br>* Other names: Navelbine and Xeloda;|
| No Intervention: Control group<br>no treatment group of Non-pCR patients after DT or ET neoadjuvant chemotherapy. No drugs treatment in this group. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR rate | pCR rate in the DT and ET group | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of neo-adjuvant chemotherapy | 5-year DFS in the DT and ET group | 5 years | 
| Efficacy of sequential chemotherapy | 5-year DFS of non- pCR patients treated by sequential NX regimen | 6 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, neoadjuvant chemotherapy,susceptible gene