Hormone Receptor-Positive Breast Cancer, HER2 Low Breast Carcinoma, Early-Stage Breast Cancer
Conditions
Keywords
Culmerciclib, Hormone receptor-positive breast cancer, HER2-negative, endocrine therapy, neoadjuvant
Brief summary
This is a single-center, open-label, randomized phase II clinical trial designed to evaluate the efficacy and safety of neoadjuvant Culmerciclib combined with aromatase inhibitor versus aromatase-inhibitor monotherapy in patients with Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative early-stage breast cancer.
Interventions
DRUGCulmerciclib
24 weeks of continuous oral Culmerciclib 180 mg once daily ，continuously
Anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg, administered orally once daily continuously
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen 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
* Able to understand study procedures, voluntarily participate in the study, and provide written informed consent. * Female patients aged ≥18 and ≤70 years with histopathologically confirmed untreated unilateral primary invasive breast cancer. * Hormone-receptor positive (estrogen receptor immunohistochemical expression ≥10%), and HER2-negative (IHC 0-1+, or IHC 2+ with negative FISH test). * Tumor size \>2 cm or positive regional lymph nodes (TNM stage II-IIIA). * At least one measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Adequate cardiac function meeting all of the following criteria: i. 12-lead electrocardiogram shows no abnormality or clinically insignificant changes requiring no medical intervention; ii. QTc interval ≤480 ms; iii. No history of torsades de pointes or other symptomatic QTc abnormalities; iv. Left-ventricular ejection fraction (LVEF) ≥50%. * Adequate bone-marrow reserve: white blood cell count ≥3.0×10⁹/L; absolute neutrophil count ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; hemoglobin ≥90 g/L. * Adequate hepatic and renal function: AST and ALT ≤2.5 × upper limit of normal (ULN); alkaline phosphatase ≤2.5 × ULN; total bilirubin ≤1.5 × ULN; serum creatinine ≤1.5 × ULN. * For pre-menopausal females or females without surgical sterilization: agree to use effective contraception during study treatment and for at least 6 months after the last dose of study treatment.
Exclusion criteria
* Occult breast cancer, inflammatory breast cancer, Paget's disease of the breast, stage IV (metastatic) breast cancer, or bilateral breast cancer. * Known hypersensitivity to active ingredients or other excipients of study drugs. * Requirement for additional anti-tumor therapy (excluding ovarian function suppression) during neoadjuvant treatment, as judged by the investigator. * Prior hormone-replacement therapy that has not been discontinued for at least 2 weeks before study treatment initiation. * Previous history of anti-tumor chemotherapy, selective estrogen-receptor modulators, or aromatase inhibitor therapy. * Severe cardiac diseases or conditions that would preclude tolerability of study treatment, including but not limited to: i. Life-threatening arrhythmias or higher-grade atrioventricular block (Mobitz type II second-degree or third-degree atrioventricular block); ii. Unstable angina pectoris; iii. Clinically significant valvular heart disease; iv. Electrocardiogram evidence of transmural myocardial infarction; v. Poorly controlled hypertension. * Major surgery unrelated to breast cancer within 4 weeks prior to enrollment, or incomplete recovery from such surgical procedures. * Severe or uncontrolled infections that may interfere with study treatment or outcome assessment, including but not limited to active viral hepatitis, positive human immunodeficiency virus antibody, pulmonary infection. * History of other malignancies within the past 5 years (except cured carcinoma in-situ of cervix or basal-cell carcinoma of skin). * Underlying gastrointestinal disorders (especially chronic diarrhea or constipation), inability to swallow, intestinal obstruction, or other conditions interfering with drug intake and absorption. * Any other condition rendering the patient unsuitable for study participation, in the investigator's opinion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of participants achieving Residual Cancer Burden (RCB) grade 0 or 1 | Within 4 weeks after surgery | Proportion of subjects achieving RCB-0 or RCB-1 scores for tumor in the breast tumor bed and regional lymph nodes following neoadjuvant therapy, calculated using the online calculator available on the MD Anderson official website, as assessed by pathologists blinded to treatment assignment. Subjects who discontinued study treatment and received other non-protocol-specified neoadjuvant therapy prior to definitive surgery, subjects who did not undergo surgery, and subjects with missing efficacy information will be categorized as not achieving RCB-0/I (non-responders). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate | Within 4 weeks after surgery | The proportion of patients with no residual invasive tumor cells in the breast and axillary nodes, regardless of ductal carcinoma in situ |
| Objective response rate | Within 2 weeks of breast MR examination | The proportion of participants achieving complete response and partial response from the initiation of treatment until disease progression or completion of preoperative neoadjuvant therapy. According to RECIST Version 1.1, intra-breast lesions are evaluated by breast MRI at the end of Week 8 and end of week 24, and after discontinuation of study treatment (if applicable). |
| Endocrine Prognostic Index score 0 rate | Within 4 weeks after surgery | The proportion of participants achieving a score of 0 according to the standard Pre-operative Endocrine Prognostic Index (PEPI) after neoadjuvant therapy |
| Complete Cell Cycle Arrest (CCCA) rate | Within 4 weeks after surgery | Proportion of subjects with Ki67 \< 2.7% after neoadjuvant therapy |
| Breast conservation surgery rate | Within 4 weeks after surgery | The proportion of patients who had successful breast conservation surgery after neoadjuvant therapy |
| Health-related Quality of Life 1 | Within 7 days before the first treatment and the end of each cycle (each cycle is 28 days) | Scores on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30, version 3.0) are linearly transformed to a 0-100 scale for all subscales and single items. The instrument comprises functional scales (physical, role, cognitive, emotional, social), a global health status/quality-of-life scale, and symptom scales/items (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For functional and global health status scales, higher scores indicate better functioning and higher quality of life; for symptom scales, higher scores indicate worse symptoms or greater problems. |
| Health-related Quality of Life 2 | Within 7 days before the first treatment and the end of each cycle (each cycle is 28 days) | The EORTC Quality of Life Questionnaire Breast Cancer Module (QLQ-BR42) has all subscale and item scores also linearly transformed to a 0-100 scale. The module includes functional subscales (e.g., body image, sexual functioning) and symptom subscales (e.g., systemic therapy side effects, breast symptoms, arm symptoms). Higher scores on functional subscales indicate better functioning, while higher scores on symptom subscales indicate more severe symptoms or side effects. |
| 5-year event-free survival | During the 5 years after random assignment | the time from random assignment until any relapse, unequivocal tumor progression, or any-cause death |
| 5-year overall survival | During the 5 years after random assignment | the time from random assignment until any-cause death |
| Safety (AEs+SAEs) | from signing the informed consent form until 2 years after completion of neoadjuvant treatment | General safety will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Ovarian toxicity will be evaluated by menstrual status and FSH and E2 |
Countries
China
Contacts
CONTACTChang Gong
PRINCIPAL_INVESTIGATORChang Gong
Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Outcome results
None listed