A Prospective, Phase II Trial Using Circulating Tumor DNA to Initiate Post-operation Boost Therapy After Neoadjuvant Chemotherapy in Triple-negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Tislelizumab
- Conditions
- Triple-negative Breast Cancer
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 460
- Locations
- 1
- Primary Endpoint
- 5 years Disease free survival(DFS)
- Status
- Recruiting
- Last Updated
- 3 years ago
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.
Investigators
Liu Qiang
Doctor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
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
Arms & Interventions
A
ctDNA positive, non-pCR Intervention: Tislelizumab(anti-PD1 antibody) combined with capecitabine
Intervention: Tislelizumab
A
ctDNA positive, non-pCR Intervention: Tislelizumab(anti-PD1 antibody) combined with capecitabine
Intervention: capecitabine
B
ctDNA positive, non-pCR Intervention: capecitabine(standard care)
Intervention: capecitabine
C
ctDNA positive, pCR Intervention: capecitabine
Intervention: capecitabine
Outcomes
Primary Outcomes
5 years Disease free survival(DFS)
Time Frame: 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 Outcomes
- objective response rate(ORR)(12 months)
- pathological complete remission(pCR) rate(12 months)
- brain metastasis rate(60 months)
- 10 years OS(120 months)
- 5 years overall survival(OS)(60 months)
- Number of Patients with Adverse Events as a Measure of Safety and Tolerability(12 months)
- 10 years DFS(120 months)
- Relapse and metastasis rate(24 months)