Clinical trial NCT05753618: Evaluating Omission of Granulocyte Colony-stimulating Factors in Breast Cancer Patients Receiving Paclitaxel Portion of Dose-dense Adriamycin-cyclophosphamide and Paclitaxel Chemotherapy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Early-stage Breast Cancer
Keywords: Filgrastim
Pegfilgrastim
Bone pain
Paclitaxel
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2023-03-03
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Patient-reported bone pain during cycle 1 of paclitaxel
timeFrame: At the end of cycle 1 of paclitaxel chemotherapy (each cycle is 14 days)
Secondary outcomes:
measure: Patient-reported bone pain across all paclitaxel cycles
timeFrame: After each of the paclitaxel chemotherapy cycles (each cycle is 14 days)
measure: Peak bone pain experienced
timeFrame: Days 1 to 5 of the each of the paclitaxel chemotherapy cycles (each cycle is 14 days)
measure: Patient health-related quality of life
timeFrame: Through study completion, average of 12 weeks
measure: Rates of completion of 4 cycles of paclitaxel
timeFrame: Through study completion, average of 12 weeks
measure: Dose-intensity of paclitaxel chemotherapy
timeFrame: Through study completion, average of 12 weeks
measure: Incidence of febrile neutropenia/neutropenia
timeFrame: Through study completion, average of 12 weeks
measure: Incidence of treatment-related hospitalizations/ER visits
timeFrame: Through study completion, average of 12 weeks
measure: Healthcare resource utilization: Emergency Room Visits
timeFrame: Through study completion, average of 12 weeks
measure: Healthcare resource utilization: Planned and Unplanned Provider Visits
timeFrame: Through study completion, average of 12 weeks
measure: Healthcare resource utilization: Phone Calls and Emails
timeFrame: Through study completion, average of 12 weeks
measure: Cost-effectiveness ratios
timeFrame: Through study completion, average of 12 weeks
measure: Incidence of chemotherapy-related mortality
timeFrame: Through study completion, average of 12 weeks
measure: Rate of secondary G-CSF or antibiotic use
timeFrame: Through study completion, average of 12 weeks
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Xinni Song, MD
role: PRINCIPAL_INVESTIGATOR
References: