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

Early-stage Breast Cancer Clinical Trial

— AMENDER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05345860
• Other study ID #: NCC3397
• Status: Recruiting
• Phase: N/A
• Start date: March 24, 2022
• Est. completion date: March 24, 2027

Study information

• Verified date: April 2022
• Source: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Contact: Fei Ma
• Phone: 86-10-87788060
• Email: drmafei[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: March 24, 2027
• Est. primary completion date: March 24, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Early-stage Breast Cancer

Intervention

Other:
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Beijing Huanxing Cancer Hospital	Beijing	Beijing
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Cancer Hospital, Chinese Academy of Medical Sciences, Hebei Center	Langfang	Hebei

Sponsors (3)

Lead Sponsor	Collaborator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing Huanxing Cancer Hospital, Cancer Hospital, Chinese Academy of Medical Sciences, Hebei Center

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time from MRD turning positive until clinical relapse	the mean time from MRD turning positive until clinical relapse	Up to 5 years
Other	Coincidence rate between MRD continuing positive and clinical relapse	the coincidence rate between MRD continuing positive and clinical relapse	Up to 5 years
Primary	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	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
Secondary	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
Secondary	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
Secondary	Adverse events (AEs)	The drug safety was assessed by investigator(s) according to NCI-CTCAE v5.0.	Up to 5 years
Secondary	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
Secondary	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