De-escalation Therapy in Stage I ER-Positive Breast Cancer: A Non-Inferiority Trial

NCT07153757 | Not Yet Recruiting Phase 3

• 1 other identifier: SCHBCC-N097
• Study Type: interventional
• Target: 2,934
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, randomized, open-label, non-inferiority Phase III clinical trial, planning to enroll 2,934 patients, with a 1:1 allocation to either the conventional endocrine therapy group or the de-escalation therapy group. The aim is to evaluate the safety and efficacy of 2-3 years of de-escalated endocrine therapy in patients with T1N0M0 potentially low-risk breast cancer, respectively.

Conditions

Breast Cancer Early Stage Breast Cancer (Stage 1-3)

Outcome Measures

Primary Outcomes (1)

• 5-year disease-free survival in the per-protocol population

  The proportion of patients in a clinical trial who remained free of disease recurrence, secondary primary cancers, and death from the disease for five years following treatment initiation, calculated specifically among those who completed the study intervention as predefined in the trial protocol(i.e., without major deviations such as incomplete treatment, use of prohibited therapies, or significant protocol violations).

  5 year

Secondary Outcomes (5)

• 5-year disease-free survival in the Full Analysis Set

  5 year

• 5-year invasive breast cancer-free survival in the per-protocol population

  5 year

• Overall survival in the per-protocol population

  5 year

• Quality of Life score in the per-protocol population

  5 year

• safety

  5 year

Study Arms (2)

5 years of standard endocrine therapy

ACTIVE COMPARATOR

The control group receives 5 years of standard endocrine therapy: Premenopausal patients: Tamoxifen (10 mg, orally, twice daily, for 5 years) or Toremifene (60 mg, orally, once daily, for 5 years); Postmenopausal patients: Letrozole (2.5 mg, orally, once daily, for 5 years) or Anastrozole (1 mg, orally, once daily, for 5 years) or Exemestane (25 mg, orally, once daily, for 5 years); A sequential regimen of 2-3 years of Tamoxifen or Toremifene followed by 3-2 years of Letrozole, Anastrozole, or Exemestane is acceptable. Ovarian function suppression is permitted for premenopausal patients. CDK4/6 inhibitors are not allowed during the treatment course

Drug: Endocrine Therapy of Physician's Choice

2-3 years of de-escalated endocrine therapy

EXPERIMENTAL

The experimental group receives 2-3 years of endocrine therapy: Premenopausal patients: Tamoxifen (10 mg, orally, twice daily, for 2-3 years) or Toremifene (60 mg, orally, once daily, for 2-3 years); Postmenopausal patients: Letrozole (2.5 mg, orally, once daily, for 2-3 years) or Anastrozole (1 mg, orally, once daily, for 2-3 years) or Exemestane (25 mg, orally, once daily, for 2-3 years). Ovarian function suppression is permitted for premenopausal patients. CDK4/6 inhibitors are not allowed during the treatment course.

Drug: Endocrine Therapy of Physician's Choice

Interventions

Endocrine Therapy of Physician's Choice DRUG

This study employs a 2-3 year de-escalated endocrine therapy regimen in the experimental group, which distinguishes it from other escalation therapy studies.

2-3 years of de-escalated endocrine therapy; 5 years of standard endocrine therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females aged 18 years or older;
• Postoperative pathological stage I early breast cancer: histologically confirmed invasive carcinoma with a maximum diameter ≤2 cm and node-negative (N0);
• Immunohistochemistry (IHC) shows ER-positive (ER ≥50%), HER2 IHC score of 0, 1+, or 2+ with no amplification confirmed by FISH, and Ki-67 ≤20%;
• Presence of at least one of the following potential low-risk factors:
• ）Tumor size ≤1 cm, 2）21-gene recurrence score \<11, 3）Fudan digital pathological subtype classified as SNF1, 4）Age ≥65 years;
• ECOG performance status of 0 or 1;
• Patients with bilateral synchronous invasive lesions are eligible if both lesions are ER-positive, HER2-negative, and meet the tumor size criteria;
• Normal major organ function, meeting the following criteria:
• Hematological: HB ≥90 g/L (no transfusion within 14 days), ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L;
• Biochemical: TBIL ≤1.5×ULN, ALT and AST ≤3×ULN, serum Cr ≤1×ULN, and creatinine clearance \>50 mL/min (Cockcroft-Gault formula);
• Participants voluntarily enroll, sign informed consent, demonstrate good compliance, and cooperate with follow-up.

You may not qualify if:

• Primary tumor size \>2 cm in maximum diameter and/or axillary lymph node positivity;
• Prior neoadjuvant therapy, any systemic therapy, or local therapy (except surgery), including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy;
• Prior adjuvant chemotherapy;
• Use of CDK4/6 inhibitors in the adjuvant setting;
• History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);
• Metastasis at any site;
• Pregnancy, lactation, or women of childbearing potential unable to use effective contraception;
• Concurrent participation in other clinical trials;
• Severe cardiac, pulmonary, hepatic, or renal dysfunction; LVEF \<50% (by echocardiography); severe cardio-cerebrovascular diseases within 6 months (e.g., unstable angina, chronic heart failure, uncontrolled hypertension \>150/90 mmHg, myocardial infarction, or stroke); poorly controlled diabetes; severe hypertension;
• Severe or uncontrolled infections;
• History of drug abuse or psychiatric disorders;
• Patients deemed unsuitable for the study by the investigator.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

270 Dongan Road, Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Arm#1: 5 years of standard endocrine therapy； Arm#2: 2-3 years of de-escalated endocrine therapy

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 4, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2033
• Study Completion (Estimated): September 1, 2033
• Last Updated: September 4, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)