A Multicenter Open-label Non-comparative 2-Stage Phase 1a/1b Study to Assess the Safety and Pharmacokinetics of BCD-115 (JSC BIOCAD, Russia) in Combination With Endocrine Therapy in Women With ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biocad
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration (Cmax)
研究概览
简要总结
A Multicenter Open-label Non-comparative 2-Stage Phase 1a/1b Study to Assess the Safety and Pharmacokinetics of Oral BCD-115 (JSC BIOCAD, Russia) in Combination with Endocrine Therapy in Women with ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer
详细描述
Multicentre dose-finding open-label non-comparative phase Ia/Ib clinical trial for investigation of the safety, tolerability, pharmacokinetics of BCD-115 administered p.o. with intrapatient dose escalation in the population of patients with ER(+) HER2(-) advanced breast cancer in combination with a standard dose of endocrine therapy.
The trial will be conducted in two stages:
Stage 1 - finding of the maximum tolerated dose, determination of the recommended dose for Stage 2.
Stage 2 - study of the recommended dose from Stage 1 of BCD-115, analysis of tolerability and safety of selected dose/doses in additional cohorts, and determination of the estimated therapeutic dose/doses for further clinical studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent and ability to follow the Protocol procedures;
- •Age ≥18 years;
- •Female gender;
- •Postmenopausal status (Prior bilateral surgical oophorectomy; or medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause);
- •Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease;
- •Progression of advanced breast cancer on first line endocrine therapy for advanced breast cancer.
- •ER positive tumor ≥ 10%;
- •HER2 negative breast cancer by FISH or IHC;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 -2
- •Measurable disease according to RECIST 1.1 (only bone disease is not allowed)
- •Resolution of all acute toxic effects of prior therapy (including endocrine therapy) or surgical procedures to CTCAE grade ≤1
- •Adequate organ function;
- •Life expectancy - 12 weeks or more from the moment of randomization
排除标准
- •HER2-positive tumour ;
- •Patients with unstable brain metastases, advanced, symptomatic, visceral spread disease, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions pleural, pericardial, peritoneal, pulmonary lymphangitis, and over 50% liver involvement).
- •Important cardiovascular events in the past 6 months to randomization;
- •GI diseases which may affect the absorption of the study drug;
- •Inadequate hematopoietic function: neutrophils ≤1500/mm3, platelets ≤100 000/mm3,or hemoglobin ≤90 g/L;
- •Inadequate renal function: creatinine level ≥ 1.5 × upper limit of normal (ULN);
- •Inadequate liver function: bilirubin level ≥ 1.5 × ULN, AST and ALT levels ≥ 2.5 × ULN (5 × ULN for patients with liver metastases), alkaline phosphatase level ≥ 5 × ULN;
- •Concurrent antitumor treatment 21 days before randomization (surgery, radiation therapy; chemotherapy, except endocrine therapy);
- •Any other concomitant cancer including contralateral breast cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;
- •Conditions limiting patient's adherence to protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
- •Concomitant participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;
- •Acute or active chronic infections;
- •HCV, HBV, HIV or syphilis infections;
- •Obstacles to p.o. administration of study drug.
研究组 & 干预措施
BCD-115 in dose escalation regimen
BCD-115 will be administered p.o. with intrapatient dose escalation in the population of patients with ER(+) HER2(-) advanced breast cancer in combination with a standard dose of endocrine therapy.
干预措施: BCD-115 (Drug)
结局指标
主要结局
Peak Plasma Concentration (Cmax)
时间窗: 90 days
To determine observed maximum concentration in plasma or serums after single doses of BCD-115 p.o. administration with dose
The incidence and severity of AEs
时间窗: 90 days
The incidence and severity of AEs (%) related with the therapy based on results of review by 3 experts (%)
The incidence of grade 3-4 AEs
时间窗: 90 days
The incidence of grade 3-4 AEs (%) related with the therapy based on results of review by 3 experts
Area under the plasma concentration versus time curve (AUC0-t)
时间窗: 90 days
To determine AUC0-t after single doses of BCD-115 p.o. administration with dose escalation;
次要结局
- Treatment discontinuation due to adverse events(90 days)