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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Triple-negative Breast Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: capecitabine

• Study Type: Interventional
• Enrollment (Anticipated): 460
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shunying Li, MD; Phone Number: +86-15915939702; Email: lishunying@foxmail.com
• Study Contact Backup: Name: Yudong Li, MD; Phone Number: 020-34071156; Email: 910870698@qq.com

Study Locations

• China
  • Guangdong
    • Guandong, Guangdong, China
      • Recruiting
      • Sunyat-sen Memorial Hospital
      • Contact: shunying Li; Phone Number: +86-15915939702; Email: lishunying@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Qiang Liu, MD, Sunyat-sen Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2020
• Primary Completion (Anticipated): August 1, 2027
• Study Completion (Anticipated): August 1, 2032

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: SunYatsenU2H-LQ3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No