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

NCT ID: NCT05345860

Last Updated: 2022-04-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-24
• Study Completion Date: 2027-03-24

Brief Summary

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

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.

Conditions

Early-stage Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TNBC with high risk or MRD+

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.

Group Type: EXPERIMENTAL

The MRD strategy for high risk or MRD+ TNBC patients

Intervention Type: OTHER

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.

HER2+ with high risk or MRD+

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.

Group Type: EXPERIMENTAL

The MRD strategy for high risk or MRD+ HER2+ patients

Intervention Type: OTHER

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.

ER+ with high risk or MRD+

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.

Group Type: EXPERIMENTAL

The MRD strategy for high risk or MRD+ ER+ patients

Intervention Type: OTHER

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.

TNBC with low risk and MRD-

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.

Group Type: EXPERIMENTAL

The MRD strategy for low risk and MRD- TNBC patients

Intervention Type: OTHER

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.

HER2+ with low risk and MRD-

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.

Group Type: EXPERIMENTAL

The MRD strategy for low risk and MRD- HER2+ patients

Intervention Type: OTHER

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.

ER+ with low risk and MRD-

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.

Group Type: EXPERIMENTAL

The MRD strategy for low risk and MRD- ER+ patients

Intervention Type: OTHER

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.

Interventions

The MRD strategy for high risk or MRD+ TNBC patients

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.

Intervention Type: OTHER

The MRD strategy for high risk or MRD+ HER2+ patients

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.

Intervention Type: OTHER

The MRD strategy for high risk or MRD+ ER+ patients

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.

Intervention Type: OTHER

The MRD strategy for low risk and MRD- TNBC patients

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.

Intervention Type: OTHER

The MRD strategy for low risk and MRD- HER2+ patients

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.

Intervention Type: OTHER

The MRD strategy for low risk and MRD- ER+ patients

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.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Beijing Huanxing Cancer Hospital

OTHER

Sponsor Role: collaborator

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Ma Fei，MD

Deputy Director of Medical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fei Ma

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Beijing Huanxing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Cancer Hospital, Chinese Academy of Medical Sciences, Hebei Center

Langfang, Hebei, China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Fei Ma

Role: CONTACT

drmafei@126.com

86-10-87788060

Hongnan Mo

Role: CONTACT

86-10-87788120

Facility Contacts

Fei Ma

Role: primary

drmafei@126.com

86-10-87788060

Xiaoying Sun

Role: primary

15910905228

Kaiping Ou

Role: primary

8615901262958

Other Identifiers

NCC3397

Identifier Type: -

Identifier Source: org_study_id