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

Phase 2

Recruiting

• Conditions: Triple-negative Breast Cancer
• Interventions: Drug: Tislelizumab; Drug: capecitabine

• Registration Number: NCT04501523
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-08-03
• Study First Submitted: 2020-08-03
• Study First Submitted QC: 2020-08-05
• Study First Posted: 2020-08-06
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-16
• Last Update Posted: 2023-02-21
• Primary Completion: 2027-08
• Study Completion: 2032-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 460

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Tislelizumab	ctDNA positive, non-pCR Intervention: Tislelizumab(anti-PD1 antibody) combined with capecitabine
A	capecitabine	ctDNA positive, non-pCR Intervention: Tislelizumab(anti-PD1 antibody) combined with capecitabine
B	capecitabine	ctDNA positive, non-pCR Intervention: capecitabine(standard care)
C	capecitabine	ctDNA positive, pCR Intervention: capecitabine

Primary Outcome Measures

Name	Time	Method
5 years Disease free survival(DFS)	60 months	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

Secondary Outcome Measures

Name	Time	Method
objective response rate(ORR)	12 months	The percentage of patients who achieved PR+CR
pathological complete remission(pCR) rate	12 months	pathological complete remission
brain metastasis rate	60 months	The percentage of patients who develop brain metastasis
10 years OS	120 months	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
5 years overall survival(OS)	60 months	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
Number of Patients with Adverse Events as a Measure of Safety and Tolerability	12 months	To determine the toxicities associated with tislelizumab in this population
10 years DFS	120 months	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
Relapse and metastasis rate	24 months	The percentage of patients who develop brain metastasis any relapse or metastasis

Trial Locations

Locations (1)

Sunyat-sen Memorial Hospital; 🇨🇳 Guandong, Guangdong, China