Breast Cancer
Conditions
Keywords
Luminal breast cancer, non-inferiority trial
Brief summary
This study is a Phase III non-inferiority trial targeting a specific subset of early breast cancer patients: those with HR-positive/HER2-negative, node-negative small tumors (typically ≤2cm) but who exhibit high-risk features for recurrence (such as high histological grade, high Ki-67 index, etc.). Currently, the standard adjuvant treatment for these patients often includes chemotherapy followed by endocrine therapy, despite their small tumor size, due to the high-risk biological characteristics. However, chemotherapy can bring significant toxicity and long-term side effects. This trial explores whether a chemotherapy-sparing approach is feasible. It compares the efficacy and safety of using the CDK4/6 inhibitor Dalpiciclib combined with endocrine therapy (AI ± OFS) directly, without chemotherapy, against the traditional approach of chemotherapy (TC regimen) followed by endocrine therapy. The primary goal is to demonstrate that the chemotherapy-free regimen is not inferior to the chemotherapy-containing regimen in terms of 5-year invasive disease-free survival (iDFS). If successful, this study could potentially de-escalate treatment for this high-risk population, sparing them from chemotherapy-related toxicities while maintaining excellent oncological outcomes.
Interventions
DRUGDalpiciclib+AI ± OFS
Chemotherapy-free regimen Dalpiciclib 125mg qd d1-d21 Q4W orally for 2 years Combined with AI (at least 5 years) ± OFS
DRUGTC (Docetaxel + Cyclophosphamide) × 4 cycles- endocrine therapy
TC (Docetaxel + Cyclophosphamide) × 4 cycles Endocrine therapy according to current indications and physician's choice
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Female, aged 18 to 70 years. 2. Histologically confirmed early breast cancer with pathological stage T1N0, 0.5 cm \< tumor size ≤ 2 cm, ER-positive/HER2-negative, with ER expression ≥ 50%; and willingness to receive adjuvant dalpiciclib treatment. 3. Presence of at least one of the following high-risk features: Ki-67 index ≥ 50%; Grade 3 (G3) tumor; an indication for chemotherapy based on results from multigene assays, including the 21-gene recurrence score and the 70-gene signature ; Age ≤ 40 years. 4. ECOG performance status: 0 to 1. 5. Adequate organ function, defined as meeting the following criteria: Hematology (no blood transfusion within 14 days): Hemoglobin (HB) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelet (PLT) ≥ 100 × 10⁹/L. Biochemistry: Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × ULN; Serum Creatinine (Cr) ≤ 1 × ULN, with creatinine clearance \> 50 mL/min (calculated using the Cockcroft-Gault formula). 6. Voluntary participation with written informed consent, good compliance, and willingness to comply with follow-up requirements.
Exclusion criteria
1. Patients who have received neoadjuvant therapy, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy. 2. Bilateral breast cancer. 3. History of other prior malignancies, except for curatively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix. 4\) Evidence of metastasis at any site. 5) Any T4 lesion (UICC 1987), including skin involvement, tumor fixation/mass, or inflammatory breast cancer. 6\) Pregnant or lactating women, or women of childbearing potential who are unwilling to use adequate contraception. 7\) Concurrent participation in another clinical trial. 8) Severe organ dysfunction (cardiac, pulmonary, hepatic, or renal). Left Ventricular Ejection Fraction (LVEF) \< 50% (by echocardiography). History of severe cardiovascular or cerebrovascular disease within 6 months prior to randomization (e.g., unstable angina, chronic heart failure, uncontrolled hypertension \>150/90 mmHg, myocardial infarction, or cerebrovascular accident). Patients with poorly controlled diabetes mellitus or severe hypertension. 9\) Known hypersensitivity to taxanes or their excipients. 10)Severe or uncontrolled infection. 11)History of psychoactive substance abuse that cannot be discontinued, or history of mental disorders. 12)Patients deemed by the investigator to be unsuitable for participation in this study. 13)Patient refusal to receive adjuvant dalpiciclib treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| iDFS | 5 years | It is defined as the percentage of patients who remain free of invasive disease recurrence, secondary primary invasive cancers, or death from any cause over a 5-year period from randomization or initiation of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DFS | 5 years | It measures the proportion of patients who remain free of detectable disease (including recurrence, progression, or new primary cancer) and alive for 5 years after starting treatment or randomization. |
| DDFS | 5 years | 5-year DDFS is an oncology clinical trial endpoint that specifically measures the proportion of patients who remain free of distant metastasis (spread of cancer to remote organs) and death from the cancer within 5 years after initiation of study treatment or randomization. It focuses exclusively on distant metastatic events rather than all disease recurrences. |
| RFS | 5 years | 5-year RFS is an oncology clinical trial endpoint that measures the proportion of patients who remain free of disease recurrence (local, regional, or distant) for 5 years following curative-intent treatment (typically surgery). It specifically focuses on recurrence of the original primary cancer and does not include new primary cancers unrelated to the initial diagnosis. |
| OS | 5 years | Overall Survival (OS) is the gold standard efficacy endpoint in oncology clinical trials, defined as the time from randomization (or treatment initiation) to death from any cause. It represents the most objective and clinically meaningful measure of treatment benefit, directly reflecting whether a therapy prolongs patients' lives. |
| Safety and Tolerability | 5 years | Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 5.0) Toxicity Reporting Criteria. |
| Quality of Life score in the per-protocol population | 5 years | The quality of life of patients was assessed using the EORTC QLQ-C30 questionnaire before, during, and after treatment. |
Contacts
CONTACTZhimin Shao Professor
Outcome results
None listed