A Single-Center, Open-Label, Dose-Escalation Phase I Clinical Trial of Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein for Injection as an Adjuvant to Chemotherapy in Subjects With Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 主要终点
- Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.
研究概览
简要总结
A Phase I, dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of F-627 in female breast cancer patients who received up to 4 cycles of Epirubicin and Cyclophosphamide. 18 patients (6 patients each cohort) were assigned to three escalated dose cohorts of 80, 240 and 320 µg/kg.
详细描述
A Phase I, dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of F-627 in female breast cancer patients receiving 4 cycles of EC (Epirubicin plus Cyclophosphamide) chemotherapy.
18 patients (6 patients each cohort) were assigned to three sequential doses cohort of F-627 at the dose of 80, 240 and 320 µg/kg. The patients received chemotherapy (100 mg/m^2 epirubicin and 600 mg/m^2 cyclophosphamide) administrated by i.v. injection on Day 1 and F-627 by s.c. injection on Day 3 of each cycle for 4 cycles. If no dose-limiting toxicity (DLT) was observed in 6 patients during first cycle, the next cohort was escalated.
Blood samples were collected for completed blood counts with differential, serum F-627 concentration and safety evaluation at different point following F-672 injection.
The decision to proceed to the next higher dose was made jointly by the sponsor's medical expert and the investigator based upon the review of safety data in the first cycle treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •18-75 years old.
- •Female postoperative breast cancer patients who require adjuvant chemotherapy, and are planned to receive 4 cycles of EC chemotherapy;
- •East Cooperative Oncology Group (ECOG) performance 0-
- •Absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L, hemoglobin (Hb) ≥ 11.0 g/dl, and platelets (PLT) ≥ 100 × 10^9/L prior to chemotherapy.
- •Hepatic and renal function within the normal range;.
- •Left ventricular ejection fraction (LVEF) > 50%.
- •Willing to sign the informed consent form and able to comply with protocol requirements
排除标准
- •Women in pregnancy or breastfeeding; Women of child-bearing potential have a positive pregnancy test result prior to the first dose;
- •Life expectancy less than 12 months;
- •Radiation therapy within 4 weeks prior to enrollment;
- •Breast cancer patients who have received neoadjuvant chemotherapy before radical mastectomy;
- •Prior bone marrow or stem cell transplant;
- •With other malignant tumors other than breast cancer;
- •Have received granulocyte colony stimulating factor (G-CSF) treatment within 6 weeks prior to enrollment;
- •Diagnosed with acute congestive heart failure, cardiomyopathy, or myocardial infarction by clinical diagnosis, electrocardiograph (ECG) or other approaches;
- •With any disease that may cause splenomegaly;
- •With acute infection, chronic active Hepatitis B within 1 year (unless patients tested negative for HBsAg prior to enrollment), or Hepatitis C;
- •History of tuberculosis (TB); history of TB exposure, unless negative for tuberculin test; TB patients undergoing treatment; or suspected TB evaluated by chest x-ray;
- •Known human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS);
- •With sickle cell anemia;
- •With alcohol or drug abuse that may affect the compliance with the study;
- •With known hypersensitivity to E. coli derived proteins, G-CSF, or excipients;
- •Has received any other investigational drug within 4 weeks prior to enrollment;
- •Patients with diseases or symptoms unsuitable for participating in the clinical trial based on the investigator's judgment;
研究组 & 干预措施
F-627 240 µg/kg
F-627 at the dose of 240 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
干预措施: F-627 (Drug)
F-627 80 µg/kg
F-627 at the dose of 80 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
干预措施: F-627 (Drug)
F-627 80 µg/kg
F-627 at the dose of 80 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
干预措施: EC regimen (Drug)
F-627 240 µg/kg
F-627 at the dose of 240 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
干预措施: EC regimen (Drug)
F-627 320 µg/kg
F-627 at the dose of 320 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
干预措施: F-627 (Drug)
F-627 320 µg/kg
F-627 at the dose of 320 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
干预措施: EC regimen (Drug)
结局指标
主要结局
Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.
时间窗: Up to 4 cycles (about 84 days)
Safety endpoints include incidence rate and severity of adverse events (AEs), laboratory measurements, physical examinations, vital signs, and performance status. Severity of AEs were assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.03 criteria.
Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.
时间窗: Up to 21 days
Tolerability should be assessed by dose-limiting toxicity (DLT). DLT is defined as any grade 3 or greater adverse event related to the investigational drug that observed in cycle 1 (21 days).
次要结局
- Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L)(Up to 4 cycles (84 days))
- Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3(Cycle 1 and cycle 3 (each cycle was about 21 days))
- Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3(Cycle 1 and cycle 3 (each cycle was about 21 days))
- T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3(Cycle 1 and cycle 3 (each cycle was about 21 days))
- Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3(Cycle 1 and cycle 3 (each cycle was about 21 days))
- Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3(Cycle 1 and cycle 3 (each cycle was about 21 days))
- Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3(Cycle 1 and cycle 3 (each cycle was about 21 days))
- Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L)(Up to 4 cycles (84 days))
- Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3(Cycle 1 and cycle 3 (each cycle was about 21 days))
- Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days)(Up to 4 cycles (84 days))
- Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L)(Up to 4 cycles (84 days))
- Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days)(Up to 4 cycles (84 days))
- Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir(Up to 4 cycles (84 days))