A Phase II, Randomized, Multi-Centre, Open-Label, Active-Controlled, Dose-Finding Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 232
- 试验地点
- 1
- 主要终点
- Duration of Moderate Neurtopenia Post First Chemotherapy Administration
研究概览
简要总结
This is a randomized open label dose finding study to evaluate the efficacy and safety of F-627 on women with Stage I-IV breast cancer receiving chemotherapy treatment.
详细描述
This is a randomized, multi-center, dose finding, open label, positive controlled Phase II study of the efficacy and safety of once-per-cycle of F-627 compared with Neulasta® (pegfilgrastim) in women with breast cancer who are receiving myelotoxic chemotherapy (TC: docetaxel + cyclophosphamide or TAC: docetaxel + doxorubicin + cyclophosphamide).
The primary objective of this study is to evaluate the efficacy and safety of various single cycle doses of F-627 as compared with the standard dosing of Neulasta® (pegfilgrastim) in breast cancer patients experiencing myelotoxic chemotherapy. Myelotoxicity in this study will be defined by the duration of moderate neutropenia; the number of days in which the patient has had an absolute neutrophil count (ANC) < 1.0 × 10^9/L during the first cycle of their chemotherapy treatment (each chemotherapy cycle is expected to last 21 days). This, by definition, includes grade 3 (moderate) and grade 4 (severe) neutropenia. Doses of F-627 to be tested for subjects receiving TC chemotherapy are 80 µg/kg/dose, 240 µg/kg/dose, and 320 µg/kg/dose. For subjects receiving TAC chemotherapy, only 240 µg/kg/dose and 320 µg/kg/dose are to be tested.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 74 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Show evidence of a signed (personally or by a legally acceptable representative) and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial.
- •Females ≥ 18 years of age.
- •Diagnosed with Stage I-IV breast cancer.
- •Subject is scheduled to undergo 4 cycles of TC or TAC chemotherapy (Taxotere®, doxorubicin and cyclophosphamide, 75, 50 and 600 mg/m2, respectively).
- •ECOG Performance status of ≤
- •White Blood Cell count (WBC) ≥ 4.0 × 109/L, hemoglobin ≥ 11.5 g/dL and a platelet count ≥ 150 × 109/L.
- •Demonstrate adequate renal, hepatic function (Liver function tests (ALT, AST, alkaline phosphatase and total bilirubin)) should be less than 2.5x upper limits of normal (ULN). Serum creatinine should be less than 1.7x ULN.
- •All subjects must agree to use at least one of the following types of contraception: intrauterine device, implantable progesterone device, progesterone intramuscular injection, or oral contraceptive, which has been started at least one month prior to visit one and will continue for the duration of the trial. The contraceptive patch or condom use with spermicide are also acceptable forms of contraception as long as they will be used continually throughout the duration of the trial.
排除标准
- •Subject is <18 or ≥ 75 years of age.
- •Disease progression has occurred while receiving a taxane regimen.
- •Subject has undergone radiation therapy within 4 weeks of enrollment.
- •Subject has undergone bone marrow or stem-cell transplantation.
- •Subject has a history of prior malignancy other than breast cancer.
- •Subjects that have used G-CSF within 6 weeks of the screening period are also excluded
- •Subject has had chemotherapy within 365 days of screening
- •Subject has documented congestive heart failure, cardiomyopathy or myocardial infarction by clinical diagnosis, ECG test, or any other relevant test.
- •History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
- •Unwillingness to participate in the study.
- •Any underlying medical condition that, in the Investigator's opinion, would make the administration of study drug hazardous to the patient or that would obscure the interpretation of adverse events.
- •Receiving other investigational drugs or biologics within 1 month or five half lives of enrollment.
- •Any condition, which can cause splenomegaly.
- •Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease.
- •ALT, AST, alkaline phosphatase > 2.5 upper limit of normal.
- •Patients with active infection, or known to be infected with chronic active Hepatitis B within the last 1 year (unless shown at the time of study entry to be Hepatitis B antigen negative), or having any history of Hepatitis C.
- •Women who are pregnant or breast-feeding.
- •Patients known to be seropositive for HIV, or who have had an AIDS defining illness or a known immunodeficiency disorder.
- •Patients with a history of tuberculosis or exposure to tuberculosis. Patients that have received a prior chest X-ray for suspicion of tuberculosis are also excluded unless they have been confirmed to be PPD negative or they had latent tuberculosis that has been previously treated.
- •Subjects with Sickle Cell disease
- •Subjects with known hypersensitivity to E.coli derived proteins' pegfilgrastim' filgrastim, or any other component of the study drug.
研究组 & 干预措施
80 µg/kg/dose of F-627
This dose of F-627 given only to subjects that are to have TC chemotherapy.
干预措施: F-627 (Drug)
240 µg/kg/dose of F-627
This dose of F-627 given to subjects receiving TC or TAC chemotherapy.
干预措施: F-627 (Drug)
320 µg/kg/dose of F-627
This dose of F-627 given to subjects receiving TC or TAC chemotherapy.
干预措施: F-627 (Drug)
Neulasta® (pegfilgrastim)
Given to subjects receiving TC or TAC chemotherapy.
干预措施: Neulasta® (pegfilgrastim) (Drug)
结局指标
主要结局
Duration of Moderate Neurtopenia Post First Chemotherapy Administration
时间窗: The first of 4, 21 Day Chemotherapy Cycles
Number of days In which the patient has had an absolute neutrophil count (ANC) Level \< 2.0 x 10\^9/L after first cycle of chemotherapy
次要结局
- The Time to ANC Recovery Post Nadir(Measured for each of the 4, 21 day chemotherapy cycles.)
- The Incidence Rates of Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles(Measured for each of the 4, 21 day chemotherapy cycles.)
- Duration in Days of Grade 3 and Grade 4 Neutropenia for All 4 Chemotherapy Cycles.(Measured for each of the 4, 21 day chemotherapy cycles.)
- The Incidence Rate of Febrile Neutropenia(Measured for each of the 4, 21 day chemotherapy cycles.)
- The Duration in Days of Total Grade 2-4 Neutropenia(Measured for each of the 4, 21 day chemotherapy cycles.)
- The Depth of the ANC Nadir for All Chemotherapy Cycles(Measured for each of the 4, 21 day chemotherapy cycles)