Adopting the MRD Strategy to Optimize Post-operation Adjuvant Therapies for Early Stage Breast Cancer

Study Overview
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Brief Summary
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This study is a prospective, multi-center, open-label cohort study, with 3 years disease free survival(DFS) as the primary endpoint. We optimize post-operation adjuvant therapy for early stage breast cancer based on the MRD strategy: patients with clinical high risk or post-operation 1st MRD tested positive will receive intensive adjuvant therapy, while patients with low clinical risk and post-operation 1st MRD tested negative will receive standard adjuvant therapy, and the treatment regimens will be adjusted every 3 months according to the change of MRD status. About 100 TNBC patients, 100 HER2+ patients, and 100 ER+ patients are planned to be enrolled.

Detailed Description
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MRD will be tested with tumor-informed personalized panel in this trail. The adjuvant therapies in the MRD strategy are all standard therapies in guidelines of China or abroad.

Official Title
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Adopting the MRD Strategy to Optimize Post-operation Adjuvant Therapies for Early Stage Breast Cancer, a Prospective Cohort Study

Conditions
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Early-stage Breast Cancer

Intervention / Treatment
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* Other: The MRD strategy for high risk or MRD+ TNBC patients
* Other: The MRD strategy for high risk or MRD+ HER2+ patients
* Other: The MRD strategy for high risk or MRD+ ER+ patients
* Other: The MRD strategy for low risk and MRD- TNBC patients
* Other: The MRD strategy for low risk and MRD- HER2+ patients
* Other: The MRD strategy for low risk and MRD- ER+ patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged ≥18 years (inclusive). Histologically confirmed, perioperative invasive breast cancer that is resectable without metastasis(stage I-III). No anti-breast cancer systematic therapy received, and planning to receive surgery and systemic therapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. With Adequate Organ Function: a. Bone marrow function: Hemoglobin ≥ 10 g/dL; Absolute leucocyte count ≥ 4×10^9/L; Absolute neutrophil count ≥ 1.5×10^9/L; Platelets ≥ 100 × 10^9/L; b. Liver function (based on the normal values specified by study site): Serum total bilirubin ≤ 1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; c. Renal function (based on the normal values specified by study site): Serum creatinine ≤ 1.5 × ULN. The patients voluntarily signed an informed consent form. Exclusion Criteria: Known to have other aggressive malignant tumor that is progressing or requires systemic treatment in the past 5 years (does not exclude subjects with skin basal cell carcinoma, skin squamous cell carcinoma, breast ductal carcinoma in situ or cervical cancer in situ that has received curative treatment). Have a clear history of neurological or mental disorders, including epilepsy or dementia, etc.; have a history of psychotropic drug abuse or drug abuse. Known history of allergy to the drug components in MRD strategy; history of immunodeficiency, or history of organ transplantation. There are other concomitant diseases that seriously threaten the patient's safety or affect the patient's completion of the study, such as serious infection, liver disease, cardiovascular disease, kidney disease, respiratory disease or uncontrolled diabetes or dyslipidemia. Female patients during pregnancy or lactation. The investigator determines that subjects are not appropriate to participate in the study due to other factors.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNBC with high risk or MRD+<br>TNBC patients with clinical high risk or post-operation 1st MRD tested positive. It's possible that this arm will be divided into many sub-arms considering the different kinds of intensive adjuvant therapies and the adopting of MRD strategy. | Other: The MRD strategy for high risk or MRD+ TNBC patients<br>* Standard adjuvant chemotherapy + additional chemotherapy: BRCA positive patients: standard adjuvant chemotherapy + olaparib BRCA negative patients: standard adjuvant chemotherapy + capecitabine In the period of once 3 months follow-up, if MRD remains positive, the additional chemotherapy will be changed for at most once.<br>|
| Experimental: HER2+ with high risk or MRD+<br>HER2+ patients with clinical high risk or post-operation 1st MRD tested positive. It's possible that this arm will be divided into many sub-arms considering the different kinds of intensive adjuvant therapies and the adopting of MRD strategy. | Other: The MRD strategy for high risk or MRD+ HER2+ patients<br>* Standard adjuvant chemotherapy + intensive targeted therapy: Neoadjuvant therapy non-pCR patients: standard adjuvant chemotherapy completed+ T-DM1/HP Neoadjuvant therapy pCR patients: standard adjuvant chemotherapy completed + HP Adjuvant therapy patients: AC-T/TCb + HP In the period of once 3 months follow-up, if MRD remains positive, the intensive targeted therapy will be changed for at most once.<br>|
| Experimental: ER+ with high risk or MRD+<br>ER+ patients with clinical high risk or post-operation 1st MRD tested positive. It's possible that this arm will be divided into many sub-arms considering the different kinds of intensive adjuvant therapies and the adopting of MRD strategy. | Other: The MRD strategy for high risk or MRD+ ER+ patients<br>* Standard adjuvant chemotherapy + intensive endocrine therapy: Premenopausal patients: Standard adjuvant chemotherapy followed by OFS + TAM/TOR, OFS + ANA/LET/EXE, or OFS + ANA/LET/EXE + Abemaciclib. Postmenopausal: Standard adjuvant chemotherapy followed by ANA/LET/EXE + Abemaciclib. In the period of once 3 months follow-up, if MRD remains positive, the intensive endocrine therapy will be changed for at most once.<br>|
| Experimental: TNBC with low risk and MRD-<br>TNBC patients with low clinical risk and post-operation 1st MRD tested negative. It's possible that this arm will be divided into many sub-arms considering the different kinds of standard adjuvant therapies and the adopting of MRD strategy. | Other: The MRD strategy for low risk and MRD- TNBC patients<br>* Standard adjuvant chemotherapy: AC-T/TC/TCb/AC. In the period of once 3 months follow-up, if MRD turns positive, additional adjuvant therapies listed in The MRD strategy for high risk or MRD+ TNBC patients will be added for at most twice.<br>|
| Experimental: HER2+ with low risk and MRD-<br>HER2+ patients with low clinical risk and post-operation 1st MRD tested negative. It's possible that this arm will be divided into many sub-arms considering the different kinds of standard adjuvant therapies and the adopting of MRD strategy. | Other: The MRD strategy for low risk and MRD- HER2+ patients<br>* Standard adjuvant chemotherapy + standard targeted therapy: Neoadjuvant therapy pCR patients: standard adjuvant chemotherapy (AC-T/TC/TCb) completed + H. Adjuvant therapy patients: AC-T/TC/TCb/wP + H. In the period of once 3 months follow-up, if MRD turns positive, additional adjuvant targeted therapies listed in The MRD strategy for high risk or MRD+ HER2+ patients will be added for at most twice.<br>|
| Experimental: ER+ with low risk and MRD-<br>ER+ patients with low clinical risk and post-operation 1st MRD tested negative. It's possible that this arm will be divided into many sub-arms considering the different kinds of standard adjuvant therapies and the adopting of MRD strategy. | Other: The MRD strategy for low risk and MRD- ER+ patients<br>* Standard adjuvant chemotherapy + standard endocrine therapy: Premenopausal patients: Standard adjuvant chemotherapy followed by TAM/TOR. Postmenopausal patients: Standard adjuvant chemotherapy followed by ANA/LET/EXE. In the period of once 3 months follow-up, if MRD turns positive, additional adjuvant endocrine therapies listed in The MRD strategy for high risk or MRD+ ER+ patients will be added for at most twice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 years disease free survival(DFS) | the period after curative treatment [disease eliminated] when no disease can be detected | From date of radical surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5 years disease free survival(DFS) | the period after curative treatment [disease eliminated] when no disease can be detected | From date of radical surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 
| 1 years disease free survival(DFS) | the period after curative treatment [disease eliminated] when no disease can be detected | From date of radical surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 
| Overall Survival(OS) | OS was defined as the time from the date of radical surgery to the date of death from any cause | From date of radical surgery until the date of death from any cause, assessed up to 60 months | 
| Adverse events (AEs) | The drug safety was assessed by investigator(s) according to NCI-CTCAE v5.0. | Up to 5 years | 
| quality of life (QoL) | QoL measurement is conducted in the hospital after treatment via digital questionnaire EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) on a tablet computer. | Up to 5 years | 
| quality of life (QoL) | QoL measurement is additionally conducted in the hospital after treatment via digital questionnaire Functional Assessment of Cancer Therapy - Breast (FACT-B) on a tablet computer. | Up to 5 years |