Multigene Risk Score Combined With Ki-67 Dynamic Assessment in Stratified Neoadjuvant Endocrine Therapy Treatment With or Without CDK4/6 Inhibitors in HR+/HER2- Breast Cancer
Phase 2
Not yet recruiting
- Conditions
- Interventions
- Registration Number
- NCT06650748
- Lead Sponsor
- Peking University
- Brief Summary
This is a prospective, single-center, randomize-controlled study. The purpose of this study is to evaluate the efficacy of neoadjuvant CDK4/6 inhibitors in patients with high-risk EPclin multigene risk analysis and non-response to Ki-67 2W, and to explore predictive biomarkers for sensitivity to CDK4/6 inhibitor therapy.
- Detailed Description
China is a country with a high incidence of breast cancer. For operable hormone receptor-positive (HR+) / human epidermal growth factor receptor 2-negative (HER2-) breast cancer, traditional neoadjuvant chemotherapy often fails to achieve clinical complete response (CCR) and has poor tolerability. Endocrine therapy plays a significant role in the treatment o...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 100
Inclusion Criteria
- Females aged 18 to 70 years;
- Patients with histologically confirmed HR+/HER2- invasive breast cancer that is sensitive to endocrine therapy. Tumor diameter >2 cm, clinically positive axillary lymph nodes not more than 2 (T2N1M0), Ki67≥+20%. Endocrine therapy sensitivity is defined as ER expression >50% by immunohistochemistry. HER-2 negativity is defined as HER-2 results of 0 or 1+ by immunohistochemistry, or negative by FISH;
- Within 28 days before the first dose of study medication, patients must have at least one measurable lesion according to RECIST 1.1 standards, as assessed by ultrasound or MRI;
- Laboratory test values: a. Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5 × 10^9/L); b. Platelet count (PLT) ≥ 100,000/mm3 (100 × 10^9/L); c. Hemoglobin (Hb) ≥ 9 g/dL (90 g/L); d. Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 30 ml/min (based on the Cockroft-Gault formula); e. Total bilirubin (BIL) ≤ 1.5 times the upper limit of normal (ULN), Gilbert's syndrome; f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤ 2.5 times the upper limit of normal (ULN); g. INR or PT ≤1.5 ULN, APTT ≤1.5 ULN.
- Subject agrees to collect tumor biopsy specimen during the screening period;
- Subject signed the informed consent form, expressing willingness and ability to comply with the planned visits, study treatments, laboratory tests, and other trial procedures.
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Exclusion Criteria
- Coexisted with other malignant tumors within 5 years prior to first medication, except for cured squamous cell carcinoma of the skin, basal cell carcinoma, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix/breast, etc;
- Had a serious infection within 1 month before screening or required systemic treatment for any active infection within 2 weeks before first medication;
- History or current presence of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis), autoimmune hepatitis, systemic sclerosis (scleroderma, etc.), Hashimoto's thyroiditis (exceptions are noted below), autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. The following exceptions apply: Type I diabetes, thyroid dysfunction requiring only hormone replacement therapy (including thyroid dysfunction caused by autoimmune thyroid disease), psoriasis or vitiligo not requiring systemic treatment;
- History of organ transplantation or allogeneic hematopoietic stem cell transplantation;
- Patients who received systemic anti-cancer treatment within 2 weeks before the first dose, including chemotherapy, immunotherapy, hormone therapy, biological therapy (cytokines or growth factors that control the progression of cancer);
- Metastatic breast cancer;
- Positive for human immunodeficiency virus antibodies (HIV-Ab) or syphilis antibodies (Anti-TP); positive for hepatitis C virus antibodies (HCV-Ab), with hepatitis C virus RNA quantification > the upper limit of the normal value of the detection unit; positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (HBcAb), with HBV DNA quantification > the lower limit of detection of the detection unit;
- History of alcohol abuse or drug abuse.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 Dalpiciclib gene high-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks Arm 1 Letrozole gene high-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks Arm 2 Letrozole gene high-risk according to Epclin who are sensitive to single-agent AI treatment for two weeks and gene low-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks, randomly assigned to letrozole treatment arm Arm 3 Dalpiciclib gene high-risk according to Epclin who are sensitive to single-agent AI treatment for two weeks and gene low-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks, randomly assigned to Dalpiciclib and letrozole treatment arm Arm 3 Letrozole gene high-risk according to Epclin who are sensitive to single-agent AI treatment for two weeks and gene low-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks, randomly assigned to Dalpiciclib and letrozole treatment arm Arm 4 Letrozole gene low-risk according to Epclin who are sensitive to single-agent AI treatment for two weeks
- Primary Outcome Measures
Name Time Method 1. The proportion of (PEPI score 0 + pCR) in patients with discordant EPclin scores and Ki67 assessments who were randomly assigned to the "+CDK4/6i" group Start of treatment until 6-month follow-up proportion of subjects who were PEPI score 0 or pCR after neoadjuvant endocrine therapy in patients with discordant EPclin scores and Ki67 assessments who were randomly assigned to the "+CDK4/6i" group
- Secondary Outcome Measures
Name Time Method The change in Ki-67 compared to the baseline after two weeks of treatment Start of treatment until 2-week follow-up The change in Ki-67 after surgery compared to two weeks post-treatment Start of treatment until 6-month follow-up Rate of patients with pCR (pathological complete response) after surgery Start of treatment until 6-month follow-up ORR Start of treatment until 6-month follow-up Objective response rate: proportion of subjects who achieved complete remission (CR) or partial remission (PR) by primary tumor imaging evaluation
CCCA rate Start of treatment until 6-month follow-up Cell cycle arrest: defined as Ki-67≤2.7%
Breast conservation rate Start of treatment until 6-month follow-up The proportion of PEPI 0-1 in patients with gene-high risk who are sensitive to single-agent AI treatment for two weeks and treated with AI in combination with Dalpiciclib Start of treatment until 6-month follow-up The proportion of PEPI 0-1 in patients with gene-low risk who are insensitive to single-agent AI treatment for two weeks and treated with AI in combination with Dalpiciclib Start of treatment until 6-month follow-up The proportion of patients at high risk according to Epclin who are downgraded to low risk after neoadjuvant treatment Start of treatment until 6-month follow-up EFS Start of treatment until 24-month follow-up Event free survival: time from the start of treatment to the first occurrence of any of the following events: disease progression, local or distant recurrence, or death due to any cause
Incidence of adverse events (AE) Start of treatment until 6-month follow-up Incidence of serious adverse events (SAE) Start of treatment until 6-month follow-up
Trial Locations
- Locations (1)
Beijing Cancer Hospital
🇨🇳Beijing, China