A Randomized Pragmatic Trial Evaluating Omission of Granulocyte Colony-stimulating Factors in Breast Cancer Patients Receiving Paclitaxel Portion of Dose-dense Adriamycin-cyclophosphamide and Paclitaxel Chemotherapy (REaCT-OGF)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 242
- 试验地点
- 6
- 主要终点
- Patient-reported bone pain during cycle 1 of paclitaxel
研究概览
简要总结
The goal of this randomized, pragmatic clinical trial is to evaluate the omission of granulocyte colony-stimulating factors (G-CSF) in breast cancer patients receiving paclitaxel portion of dose-dense adriamycin-cyclophosphamide and paclitaxel (DD-AC/T) chemotherapy. Participants will be randomized to either take G-CSF while on the paclitaxel portion of DD-AC/T chemotherapy or to omit G-CSF while on the paclitaxel portion of DD-AC/T chemotherapy.
详细描述
Optimal curative chemotherapy treatment in the early-stage setting for breast cancer patients can reduce the risk of recurrence and result in improvement in breast cancer survival. The pivotal Cancer and Leukemia Group B (CALGB) 9741 clinical trial demonstrated improved efficacy from administering 4 cycles of adriamycin and cyclophosphamide (AC) followed by 4 cycles of paclitaxel using a dose-dense schedule every 2-weeks instead of every 3 weeks in patients with high-risk early-stage breast cancer. It has since become a widely accepted standard care treatment option. Granulocyte colony-stimulating factor (G-CSF) such as filgrastim (FIL) and pegfilgrastim (PEG) are key supportive medications used with the dose-dense regimen to facilitate timely recovery of neutrophil count before the next cycle of treatment. However, G-CSF is associated with increased bone pain after chemotherapy (up to 40%) and drug-induced fever, which can result in additional clinical or emergency room visits. Clinicians have questioned if primary prophylactic G-CSF use is necessary with paclitaxel in the dose-dense regimen and the risk of hematological toxicity, such as the risk of low neutrophils and the risk of infection is lower with paclitaxel. Results from two retrospective studies suggest that it is safe and feasible to omit G-CSF during the paclitaxel portion of the DD-AC/T regimen. Based on the current trial data, there is a stong suggestion that it is safe, feasible and likely preferable to omit G-CSF during the paclitaxel portion of DD-AC/T chemotherapy. Given the majority of chemotherapy dose delays are related to issues such as bone pain (from G-CSF and paclitaxel) and peripheral neuropathy (from paclitaxel), and this may even be exacerbated by the use of G-CSF, it is anticipated that omitting G-CSF during paclitaxel chemotherapy may improve completion rates while improving health related quality of life (HR-QoL). Therefore, the researchers propose a randomized study to further evaluate patient-reported bone pain and HR-QoL from the omission of primary prophylactic G-CSF use during the paclitaxel portion of DD-AC/T chemotherapy while demonstrating supportive evidence that omitting G-CSF is safe and feasible.
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
- •Patients with early-stage or locally-advanced breast cancer receiving neoadjuvant or adjuvant DD-AC/T chemotherapy requiring primary febrile neutropenia prophylaxis with G-CSF
- •Able to provide verbal consent
- •Able to complete questionnaires in English or French
排除标准
- •No access to pegfilgrastim or filgrastim prior to randomization
- •Metastatic cancer
- •Known hypersensitivity to filgrastim or pegfilgrastim or one of its components
- •Patients received prior cytotoxic chemotherapy within the last 5 years
- •Patients with uncontrolled inter-current illness that would limit compliance with study requirements or other significant diseases or disorders that, in the investigator's opinion, would exclude the subject from participating in the study
研究组 & 干预措施
Omission of G-CSF
Omission of G-CSF injections after each cycle of paclitaxel chemotherapy.
干预措施: Omission of Granulocyte Colony-Stimulating Factor (G-CSF) (Drug)
Receive G-CSF
Receive G-CSF injections (either filgrastim or pegfilgrastim) after each cycle of paclitaxel chemotherapy.
干预措施: Granulocyte Colony-Stimulating Factor (G-CSF) (Drug)
结局指标
主要结局
Patient-reported bone pain during cycle 1 of paclitaxel
时间窗: At the end of cycle 1 of paclitaxel chemotherapy (each cycle is 14 days)
The primary outcome is patient-reported bone pain from day 1 to 5 during cycle 1 of paclitaxel chemotherapy. The total measure of bone pain over the five days will be summarized by the area under the curve (AUC) using the trapezoidal quadrature method for patients reported daily pain score from day 1 to 5 during cycle 1 of paclitaxel chemotherapy. Day 1 being the morning after first dose of G-CSF injection, or 48 hours after chemotherapy injection in the No G-CSF arm. The daily pain score ranges from 0-40. Peak pain is defined as the maximum pain rating over day 1 to day 5. To reiterate the scoring system, every morning, patients are asked to rate the most severe pain they experienced in the last 24 hours on a visual analogue scale (VAS) from 0 (no pain) to 10 (pain as bad as you can imagine). The X axis of the AUC represents time (i.e., days) and the Y axis represents pain severity (0-10).
次要结局
- Incidence of treatment-related hospitalizations/ER visits(Through study completion, average of 12 weeks)
- Incidence of chemotherapy-related mortality(Through study completion, average of 12 weeks)
- Rate of secondary G-CSF or antibiotic use(Through study completion, average of 12 weeks)
- Dose-intensity of paclitaxel chemotherapy(Through study completion, average of 12 weeks)
- Healthcare resource utilization: Planned and Unplanned Provider Visits(Through study completion, average of 12 weeks)
- Healthcare resource utilization: Phone Calls and Emails(Through study completion, average of 12 weeks)
- Patient health-related quality of life(Through study completion, average of 12 weeks)
- Rates of completion of 4 cycles of paclitaxel(Through study completion, average of 12 weeks)
- Incidence of febrile neutropenia/neutropenia(Through study completion, average of 12 weeks)
- Patient-reported bone pain across all paclitaxel cycles(After each of the paclitaxel chemotherapy cycles (each cycle is 14 days))
- Peak bone pain experienced(Days 1 to 5 of the each of the paclitaxel chemotherapy cycles (each cycle is 14 days))
- Healthcare resource utilization: Emergency Room Visits(Through study completion, average of 12 weeks)
- Cost-effectiveness ratios(Through study completion, average of 12 weeks)