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This study is a multi-center, randomized, prospective phase II clinical trial aimed at exploring and evaluating the efficacy of dalpiciclib combined with AI in neoadjuvant treatment for ER strong positive(ER≥50%),HER2-negative, Ki-67≤20%,T1-3N1M0 postmenopausal breast cancer. The primary objectives are to demonstrate non-inferiority in efficacy compared to chemotherapy and to assess its superior safety profile.
This study is a multi-center, randomized, prospective non-inferiority exploratory phase II clinical trial. Eligible subjects were randomly assigned in a 1:1 ratio to either the dalpiciclib combined with AI group (neoadjuvant endocrine group) or the AC-T group (chemotherapy group) after screening. The administration of the investigational drugs started within 48 hours after randomization. Subjects will receive either 24 weeks of dalpiciclib combined with AI or AC-T treatment until disease progression, intolerable adverse events, withdrawal of informed consent, or discontinuation by the investigator's judgment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| neoadjuvant endocrine group | Experimental | Dalpiciclib: Take 125 mg once daily for 3 weeks, then stop for 1 week. Each cycle is completed in 4 weeks. AI: Take according to the instructions provided. |
|
| neoadjuvant chemotherapy group | Active Comparator | Docetaxel for injection: Administered as a 75 mg/m2 intravenous infusion Epirubicin hydrochloride for injection: Administered as a 75 mg/m2 intravenous infusion. Cyclophosphamide for injection: Administered as a 500 mg/m2 intravenous infusion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dalpiciclib | Drug | Dalpiciclib: Take 125 mg once daily for 3 weeks, then stop for 1 week. Each cycle is completed in 4 weeks. It is recommended to take the medication approximately at the same time each day, with warm water, preferably on an empty stomach. Fasting for at least 1 hour before and after medication is advised. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Complete Radiologic Response or Partial Radiological Response: Radiological Response | Radiological response is the percentage of participants with CR or, PR according to RECIST v.1.1. A responder is defined as any participant who exhibits a CR or PR. CR is the disappearance of all target lesions. PR is a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. PD is 20% increase in the sum of diameters of target lesions taking as reference the smallest sum and the appearance of 1 or more new lesions. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, emotional, cognitive, or social functioning), global health status and symptom scales of fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| lina zhang | Contact | 15830981676 | linazh_001@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Fourth Hospital of Hebei Medical University | Recruiting | Shijiazhuang | Hebei | 050011 | China |
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| Aromatase inhibitor | Drug | AI: Take according to the instructions provided. |
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| Docetaxel injection | Drug | Administered as a 75 mg/m2 intravenous infusion over approximately 30 minutes. It is given every three weeks and dose reduction or treatment delay is allowed, up to a maximum delay of 3 weeks from the previous dose calculation. Treatment will be terminated if the delay exceeds this limit. |
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| Epirubicin Hydrochloride Injection | Drug | Administered as a 75 mg/m2 intravenous infusion. It is given every three weeks and dose reduction or treatment delay is allowed, up to a maximum delay of 3 weeks from the previous dose calculation. Treatment will be terminated if the delay exceeds this limit. |
|
| Cyclophosphamide injection | Drug | Administered as a 500 mg/m2 intravenous infusion. It is given every three weeks and dose reduction or treatment delay is allowed, up to a maximum delay of 3 weeks from the previous dose calculation. Treatment will be terminated if the delay exceeds this limit. |
|
| 6 months |
| Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index | Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. 6 variables are included in a calculation formula. | 6 months |
| Evaluation of the number of patients with PEPI 0 | PEPI stands for Preoperative Endocrine Prognostic Index. It is a scoring system used in breast cancer research to assess the response to neoadjuvant endocrine therapy. PEPI evaluates various factors, including tumor size, lymph node involvement, Ki-67 proliferation index, and estrogen receptor status, to predict the risk of recurrence and overall prognosis in patients with hormone receptor-positive breast cancer. The PEPI score helps in determining the effectiveness of neoadjuvant endocrine therapy and guiding treatment decisions. | 6 months |
| Percentage of Participants With Pathologic Complete Response (pCR) | pCR is defined as absence of invasive cancer in the breast and sampled regional lymph nodes. | 6 months |
| Calculation of the rates of breast conservation therapy in the two arms with regard to the initially planned surgery. | 6 months |
| Percent Change From Baseline to 2 Weeks in Ki67 Expression | Tumor tissue collected through a core biopsy at baseline and at the end of cycle 1 was used to determine Ki67 expression. Ki67 expression is defined as the percent of cells staining positive by validated central assay. | 2 Weeks |
| Determination of the number and type of Adverse Events as a Measure of Safety and Tolerability | The toxicity will be evaluated according to the scale CTC-AE version 5.0 | 6 months |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000720752 | dalpiciclib |
| D047072 | Aromatase Inhibitors |
| D000077143 | Docetaxel |
| D015251 | Epirubicin |
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D065088 | Steroid Synthesis Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D004965 | Estrogen Antagonists |
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D004317 | Doxorubicin |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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