RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 406
- 试验地点
- 81
- 主要终点
- Duration of Severe Neutropenia (DSN) in Cycle 1
研究概览
简要总结
The purpose of this study was to compare the efficacy of a single dose of SPI-2012 versus pegfilgrastim in participants with early-stage breast cancer receiving docetaxel and cyclophosphamide (TC), as measured by the duration of severe neutropenia (DSN) in Cycle 1.
详细描述
This was a Phase 3, randomized, open-label, active-controlled, multicenter study to compare the efficacy and safety of SPI-2012 vs pegfilgrastim in participants with breast cancer treated with TC chemotherapy.
Each cycle was 21 days. Four cycles were evaluated in this study. On Day 1 of each cycle, participants received TC chemotherapy. On Day 2 of each cycle, participants received study drug (SPI-2012 or pegfilgrastim).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer
- •Candidate for adjuvant or neoadjuvant TC chemotherapy
- •Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
- •Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
- •Platelet count ≥ 100×10^9/L
- •Hemoglobin > 9 g/dL
- •Creatinine clearance > 50 mL/min
- •Total bilirubin ≤ 1.5 mg/dL
- •Aspartate Aminotransferase per Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase per Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5× Upper Limit of Normal (ULN).
- •Alkaline phosphatase ≤ 2.0×ULN
排除标准
- •Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease
- •Locally recurrent or metastatic breast cancer
- •Known sensitivity to E. coli -derived products or to any products to be administered during dosing
- •Concurrent adjuvant cancer therapy
- •Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 12 months prior to the administration of study drug
- •Active infection, receiving anti-infectives, or any serious underlying medical condition that would impair ability to receive protocol treatment
- •Prior bone marrow or stem cell transplant
- •Use of any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study
- •Radiation therapy within 30 days prior to enrollment
- •Major surgery within 30 days prior to enrollment
研究组 & 干预措施
Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
干预措施: SPI-2012 (Drug)
Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
干预措施: Docetaxel (Drug)
Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
干预措施: Cyclophosphamide (Drug)
Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
干预措施: Pegfilgrastim (Drug)
Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
干预措施: Docetaxel (Drug)
Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Duration of Severe Neutropenia (DSN) in Cycle 1
时间窗: Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)
DSN was defined as the number of days of severe neutropenia (absolute neutrophil count \[ANC\] \<0.5×10\^9/L), after the administration of study drug in Cycle 1.
次要结局
- Number of Participants With Febrile Neutropenia (FN) in Cycle 1(Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days))
- Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1(Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days))
- Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4(Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months))
- Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1(Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days))
- Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4(Cycles 1 to 4 (each cycle was 21 days))
- Duration of Severe Neutropenia in Cycle 2, 3 and 4(Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days))
- Number of Participants With Neutropenic Complications in Cycle 1(Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days))