A Single-Arm, Phase II, Multicenter Clinical Trial to Evaluate the Efficacy of Leucogen in Preventing the Risk of Ribociclib-Associated Neutropenia in Patients With Hormone Receptor-Positive, HER2-Negative Early Breast Cancer
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Second Affiliated Hospital, School of Medicine, Zhejiang University
- 入组人数
- 94
- 主要终点
- incidence of severe neutropenia
概览
简要总结
This study is a multicenter, single-arm, open-label Phase II exploratory clinical trial designed to evaluate whether prophylactic use of leucogen can reduce the incidence of Grade 3 or higher neutropenia in early-stage HR+/HER2- breast cancer patients receiving ribociclib combined with endocrine therapy. The study plans to enroll 97 patients using a Simon two-stage design, with the primary endpoint being the incidence of severe neutropenia within 4 treatment cycles (4 months) after initiation. Secondary endpoints include the incidence of all-grade neutropenia, febrile neutropenia, ribociclib treatment intensity, and safety. The study will systematically assess the preventive efficacy and safety of leucogen to provide a basis for subsequent Phase III randomized controlled trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient has signed and dated the informed consent form.
- •Age \> 18 years at the time of signing informed consent.
- •The patient is a female with known menopausal status at the time of signing informed consent or initiation of adjuvant endocrine therapy (whichever is earlier). Postmenopausal status is defined as: bilateral oophorectomy, age \> 60 years, or age \< 60 years with amenorrhea ≥ 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression), and follicle-stimulating hormone and plasma estradiol levels within the local postmenopausal normal range.
- •Histologically confirmed unilateral primary invasive breast cancer, with the date of initial cytological or histological diagnosis within 18 months before enrollment. Patients with multicentric and/or multifocal tumors are eligible if all pathologically examined lesions meet criteria 5 and 6 below.
- •Estrogen receptor (ER) and/or progesterone receptor (PgR) positivity in the breast cancer, based on the most recent analyzed tissue sample from the local laboratory.
- •HER2-negative breast cancer, defined as negative by in situ hybridization or immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization result is required to confirm HER2-negative status (based on the most recent analyzed tissue sample from the local laboratory).
- •The patient has undergone surgical resection with complete tumor removal, negative microscopic margins on the final surgical specimen, and belongs to one of the following categories:
- •Anatomic Stage II, with any of the following: T0-2N1, T3N0, T2N0 with Grade 2 and Ki-67 ≥ 20%, T2N0 with Grade 2 and high-risk genomic assay result, T2N0 with Grade
- •Anatomic Stage III. High-risk genomic assay is defined as Oncotype DX Recurrence Score ≥ 26, or high-risk group by Prosigna PAM50, MammaPrint, or EndoPredict.
- •If clinically indicated, the patient has completed adjuvant and/or neoadjuvant chemotherapy according to guidelines before screening.
排除标准
- •Previous treatment with any CDK4/6 inhibitor.
- •Use of tamoxifen, raloxifene, or aromatase inhibitors for breast cancer risk reduction ("chemoprevention") and/or osteoporosis treatment within 2 years before signing informed consent.
- •Prior anthracycline cumulative dose reaching or exceeding: doxorubicin 450 mg/m², or epirubicin 900 mg/m².
- •Known hypersensitivity to any excipient of ribociclib and/or the endocrine therapy and/or leucogen (e.g., rare hereditary galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption, or soy allergy).
- •Evidence of distant metastasis of breast cancer beyond regional lymph nodes (AJCC 8th edition Stage IV) and/or recurrence after curative surgery.
- •Concurrent use of other anticancer therapies, except adjuvant endocrine therapy.
- •Major surgery, chemotherapy, or radiotherapy within 14 days before enrollment.
- •Clinical and laboratory acute toxicities related to prior anticancer therapy have not recovered to Grade 1 or lower (per NCI CTCAE version 4.03) on the day of enrollment. Exceptions: alopecia and amenorrhea of any grade are allowed.
- •Current invasive malignancy, or previous invasive malignancy completed treatment within 2 years before signing informed consent. Note: Patients with past or concurrent in situ malignancy are eligible if they have undergone adequate curative treatment before enrollment.
- •Known history of human immunodeficiency virus (HIV) infection.
研究组 & 干预措施
Leucogen combined with Ribociclib (Kisqali®) and Endocrine Therapy (e.g., Letrozole, Anastrozol)
The experimental arm receives ribociclib at the standard dose (orally, 400mg, once daily on days 1-21 of a 28-day cycle) combined with a specified endocrine therapy (e.g., letrozole or anastrozole) plus leucogen (40mg orally three times daily on days 8-28 of a 28-day cycle).
干预措施: Treat Regimen (Drug)
结局指标
主要结局
incidence of severe neutropenia
时间窗: From enrollment to the end of treatment at 16 weeks
Complete blood count (CBC) should be performed on Day 1 and Day 21 of each treatment cycle. A decrease in the absolute neutrophil count (ANC) to \< 1000-500/mm³ (which is equivalent to \< 1.0-0.5 × 10⁹/L) is defined as severe neutropenia.
次要结局
未报告次要终点