Phase 2, Open-Label, Dose-Ranging Study of SPI-2012 (HM10460A) or Pegfilgrastim Use for the Management of Neutropenia in Patients With Breast Cancer Who Are Candidates for Adjuvant and Neoadjuvant Chemotherapy With the Docetaxel + Cyclophosphamide (TC) Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 26
- 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 is to assess the effect of test doses of SPI-2012 on the duration of severe neutropenia (DSN) during Cycle 1 in participants with breast cancer who are candidates for adjuvant or neoadjuvant chemotherapy.
详细描述
This is an open label, multicenter, dose ranging study, sequentially enrolled by study dose, with a non-inferiority design to compare the effectiveness of SPI-2012 relative to a fixed dose of pegfilgrastim as a concurrent active control to each dose of SPI-2012 in participants with breast cancer. This study included four arms comprising three dose levels of SPI-2012 (Arm 1: 45 µg/kg, Arm 2: 135 µg/kg, Arm 3: 270 µg/kg) versus pegfilgrastim (Arm 4: 6 mg). The start of study is defined as the initiation of treatment with SPI-2012 or pegfilgrastim. The duration of treatment consists of a maximum of 4 cycles (21 days per cycle) beginning on Day 1 with chemotherapy administration and continue through Day 21, plus a 30-day follow-up period, unless any of the discontinuation criteria applies.
The target population are participants with breast cancer who are candidates for neoadjuvant or adjuvant treatment with Docetaxel + Cyclophosphamide (TC) chemotherapy. All participants who receive at least 1 dose of either SPI-2012 or pegfilgrastim were followed for safety through 30 days after their last dose of study treatment or until all treatment-related adverse events (AEs) have resolved or returned to baseline/Grade 1, whichever is longer, or until it is determined that the outcome will not change with further follow-up.
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
- •Histologically confirmed breast cancer and candidate for adjuvant or neoadjuvant chemotherapy
- •Candidate for docetaxel and cyclophosphamide chemotherapy
- •Female or male at least 18 years of age
- •Eastern Cooperative Oncology Group (ECOG) ≤ 2
- •Absolute neutrophil count (ANC) ≥ 1.5×109/L
- •Platelet count ≥ 100 x 10^9/L
- •Creatinine ≤ 1.5 x upper limit of normal (ULN)
- •Total bilirubin ≤1.5 mg/dL(≤ 25.65 μmol/L).
- •Aspartate aminotransferase per serum glutamic-oxaloacetic transaminase (AST/SGOT) and/or alanine aminotransferase per serum glutamic-pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN
- •Hemoglobin > 9 g/dL
- •Alkaline phosphatase ≤ 1.5 x ULN
排除标准
- •Known sensitivity to E. coli-derived products or known sensitivity to any of the products to be administered
- •Known Human Immunodeficiency Virus (HIV) infection
- •Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) diagnosis with detectable viral load or immunological evidence of chronic active disease
- •Active infection or any serious underlying medical condition that would impair ability to receive protocol treatment
- •Prior bone marrow or stem cell transplant
- •Prolonged exposure to glucocorticosteroids and immunosuppressive agents
研究组 & 干预措施
Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 45 microgram/kilogram (µg/kg), subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 milligram/ square metre (mg/m^2) intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: SPI-2012 (Drug)
Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 45 microgram/kilogram (µg/kg), subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 milligram/ square metre (mg/m^2) intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Docetaxel (Drug)
Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 45 microgram/kilogram (µg/kg), subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 milligram/ square metre (mg/m^2) intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Cyclophosphamide (Drug)
Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: SPI-2012 (Drug)
Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Docetaxel (Drug)
Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Cyclophosphamide (Drug)
Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: SPI-2012 (Drug)
Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Docetaxel (Drug)
Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)
Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Cyclophosphamide (Drug)
Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Participants received Pegfilgrastim 6 milligram (mg), SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Pegfilgrastim (Drug)
Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Participants received Pegfilgrastim 6 milligram (mg), SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
干预措施: Docetaxel (Drug)
Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Participants received Pegfilgrastim 6 milligram (mg), SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
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: Cycle 1 (each cycle was 21 days)
DSN was defined as the interval from the day of first observation of severe neutropenia (ANC \<0.5\*10\^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =\> 2.0\*10\^9/L in Cycle 1.
次要结局
- Time to ANC Recovery in Cycle 1(Cycle 1 (each cycle was 21 days))
- Time to ANC Recovery in Cycle 3(Cycle 3 (each cycle was 21 days))
- Duration of DSN in Cycle 2(Cycle 2 (each cycle was 21 days))
- Time to ANC Recovery in Cycle 4(Cycle 4 (each cycle was 21 days))
- Absolute ANC Nadir Overtime in Cycle 3(Cycle 3 (each cycle was 21 days))
- Duration of DSN in Cycle 3(Cycle 3 (each cycle was 21 days))
- Time to ANC Recovery in Cycle 2(Cycle 2 (each cycle was 21 days))
- Depth of ANC Nadir in Cycle 3(Cycle 3 (each cycle was 21 days))
- Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4(All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days))
- Number of Participants With Positive Antibodies for SPI-2012(Up to the end of the study (Approximately 3.5 months))
- Time to Reach Maximum Concentration of SPI-2012 (Tmax)(Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days))
- Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)(Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days))
- Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1(Cycle 1 (each cycle was 21 days))
- Depth of ANC Nadir in Cycle 2(Cycle 2 (each cycle was 21 days))
- Depth of ANC Nadir in Cycle 4(Cycle 4 (each cycle was 21 days))
- Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4(Cycle 1 to Cycle 4 (each cycle was 21 days))
- Duration of DSN in Cycle 4(Cycle 4 (each cycle was 21 days))
- Absolute ANC Nadir Overtime in Cycle 2(Cycle 2 (each cycle was 21 days))
- Depth of ANC Nadir in Cycle 1(Cycle 1 (each cycle was 21 days))
- Time to ANC Nadir in Cycle 4(Cycle 4 (each cycle was 21 days))
- Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities(From the first dose up to 30 days post last dose of study drug (up to 4 months))
- Absolute ANC Nadir Overtime in Cycle 4(Cycle 4 (each cycle was 21 days))
- Time to ANC Nadir in Cycle 1(Cycle 1 (each cycle was 21 days))
- Time to ANC Nadir in Cycle 3(Cycle 3 (each cycle was 21 days))
- Maximum Concentration of SPI-2012 (Cmax)(Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days))
- Half-life of SPI-2012 (t1/2)(Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days))
- Time to ANC Nadir in Cycle 2(Cycle 2 (each cycle was 21 days))