A Prospective, Phase II Trial Using ctDNA to Initiate Post-operation Boost Therapy After NAC in TNBC

Study Overview
=================
Brief Summary
-----------------
Positive circulating tumor DNA(ctDNA) status is associated with worse prognosis in breast cancer, especially triple-negative breast cancer(TNBC). Our trial aims to improve the outcome of TNBC patients by using ctDNA to identify patients with high relapse risk. ctDNA positive patients will be randomized to receive boost therapy or standard therapy indicated in NCCN guidelines after NAC.

Official Title
-----------------
A Prospective, Phase II Trial Using Circulating Tumor DNA to Initiate Post-operation Boost Therapy After Neoadjuvant Chemotherapy in Triple-negative Breast Cancer

Conditions
-----------------
Triple-negative Breast Cancer

Intervention / Treatment
-----------------
* Drug: Tislelizumab
* Drug: capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer, clinical stage II-III at diagnosis (AJCC 6th edition) based on initial evaluation by physical examination and/or breast imaging prior to study registration.ER and PR will be considered negative if ≤ 1% of cells stain weakly positive. HER2 will be considered negative if scored 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of < 2.0 or < 6 copies per cell. Must receive preoperative (neoadjuvant) chemotherapy. NOTE: Acceptable preoperative regimens include those recommended by NCCN guidelines. Participants who received preoperative therapy as part of a clinical trial may enroll. ctDNA positive at baseline, after NAC or after surgery Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 Written informed consent to provide research blood samples and tumor samples Patients must be willing to have frequent blood tests (every 3 months ) and receive a 12 month course of tislelizumab if randomised to tislelizumab treatment on ctDNA detection No evidence of distant metastatic disease on staging scans conducted at the time of diagnosis Exclusion Criteria: Previously participated in other interventional trials Previous malignancy within 3 years of breast cancer diagnosis Pregnancy or breastfeeding No written consent Unable to receive standard NAC and subsequent radiotherapy(if needed) Active autoimmune disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>ctDNA positive, non-pCR Intervention: Tislelizumab(anti-PD1 antibody) combined with capecitabine | Drug: Tislelizumab<br>* 200mg, q3w, for 1 year<br>Drug: capecitabine<br>* 600-750 mg/m2 PO Bid，continuous, for 1 year<br>|
| Active Comparator: B<br>ctDNA positive, non-pCR Intervention: capecitabine(standard care) | Drug: capecitabine<br>* 600-750 mg/m2 PO Bid，continuous, for 1 year<br>|
| Experimental: C<br>ctDNA positive, pCR Intervention: capecitabine | Drug: capecitabine<br>* 600-750 mg/m2 PO Bid，continuous, for 1 year<br>|
| No Intervention: D<br>Follow up(standard care) | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5 years Disease free survival(DFS) | From diagnosis to 5yrs or DFS events; To determine 5-year disease free survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5 years overall survival(OS) | From diagnosis to 5yrs or death; To determine 5-year overall survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy | 60 months | 
| pathological complete remission(pCR) rate | pathological complete remission | 12 months | 
| brain metastasis rate | The percentage of patients who develop brain metastasis | 60 months | 
| objective response rate(ORR) | The percentage of patients who achieved PR+CR | 12 months | 
| Number of Patients with Adverse Events as a Measure of Safety and Tolerability | To determine the toxicities associated with tislelizumab in this population | 12 months | 
| 10 years DFS | To determine 10-year disease free survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy | 120 months | 
| 10 years OS | To determine 10-year overall survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy | 120 months | 
| Relapse and metastasis rate | The percentage of patients who develop brain metastasis any relapse or metastasis | 24 months |