A Randomized, Multicenter Pragmatic Trial Comparing Bone Pain From a Single Dose of Pegfilgrastim to 5 Doses of Daily Filgrastim in Breast Cancer Patients Receiving Neoadjuvant/Adjuvant Chemotherapy

Study Overview
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Brief Summary
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REaCT-5G will compare bone pain from a single dose of Pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy.

Detailed Description
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The use of granulocyte colony-stimulating factors (G-CSF) significantly reduces febrile neutropenia (FN) risk and has helped maintain dose intensity and dose density when treating breast cancer with chemotherapy. This is crucial as survival outcomes are significantly impaired if dose intensity are reduced. National and international guidelines recommend the use of G-CSF as primary prophylaxis with most commonly used breast cancer chemotherapy regimens. Filgrastim (FIL) as a G-CSF that has been in use since the early 90s. Pegfilgrastim (PEG) is a long-acting, pegylated version of FIL that requires only one injection per chemotherapy cycle instead of daily FIL injections for 5 to 10 days per cycle. PEG and FIL both come at the potential cost of bone pain, the most common side effect. G-CSF related bone pain is often severe, leading to refusal or cancellation of G-CSF and early discontinuation of chemotherapy. We propose to perform a pragmatic, multicenter, open-label, randomized clinical trial to compare bone pain experienced by patients receiving either PEG or 5-day-FIL with neoadjuvant or adjuvant chemotherapy.

Official Title
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A Randomized, Multicenter Pragmatic Trial Comparing Bone Pain From a Single Dose of Pegfilgrastim to 5 Doses of Daily Filgrastim in Breast Cancer Patients Receiving Neoadjuvant/Adjuvant Chemotherapy (REaCT-5G)

Conditions
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Early-stage Breast Cancer

Intervention / Treatment
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* Drug: Filgrastim
* Drug: Pegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with early-stage or locally-advanced breast cancer receiving neoadjuvant or adjuvant 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5 Days of Filgrastim<br>Receive filgrastim subcutaneous injection once daily for five consecutive days starting 24-72 hours after chemotherapy. | Drug: Filgrastim<br>* Receive filgrastim subcutaneous injection once daily for five consecutive days starting 24-72 hours after chemotherapy<br>* Other names: Neupogen;|
| Active Comparator: Pegfilgrastim<br>Receive pegfilgrastim as a single dose subcutaneous injection 24-72 hours after chemotherapy | Drug: Pegfilgrastim<br>* Receive pegfilgrastim as a single dose subcutaneous injection 24-72 hours after chemotherapy<br>* Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone pain | Bone pain over the first 5 days after the administration of G-CSF. The total measure of bone pain over the five days will be summarized by the area under the curve (AUC) based on a patient's daily pain score, starting after the first dose of G-CSF injection. | 5 days after first G-CSF injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Febrile Neutropenia | Number of times participants have Febrile neutropenia during chemotherapy treatment | 2.5 years after study initiation | 
| Incidence of treatment-related hospitalizations | Number of times participants have a treatment-related hospitalization | 2.5 years after study initiation | 
| Incidence of chemotherapy alteration | Number of times participants have a chemotherapy alteration including: dose delay, reduction and/or discontinuation | 2.5 years after study initiation | 
| Incidence of chemotherapy-related mortality | Number of times there is a chemotherapy-related mortality | 2.5 years after study initiation | 
| Rate of G-CSF compliance as prescribed | Number of times there is a G-CSF compliance | 2.5 years after study initiation | 
| Differences in healthcare resource utilization | Differences in healthcare resource utilization: number of emergency room visits, number of planned/unplanned provider clinic visits (including stretcher bay), patient-reported phone calls or email to patient support line or provider, and additional medication use or management strategies related to G-CSF side effects or efficacy | 2.5 years after study initiation | 
| HR-QoL | HR-QoL based on EQ-5D-5L | 2.5 years after study initiation | 
| Cost-effectiveness | Cost differences associated with prescribing Filgrastim and Pegfilgrastim | 2.5 years after study initiation | 
| Patient G-CSF preference | To survey patient preference in selection of G-CSF treatment before and after undergoing chemotherapy and G-CSF treatment | 2.5 years after study initiation | 
| Study feasibility | Interim analysis/feasibility. After the first year of study initiation, if study recruitment is less than 30% at one year (70 patients), or if there are unanticipated safety issues, a review of study conduct will be performed to consider stopping the study unless there are unexpected or exceptional reasons, or in the case of low recruitment, there is a plan to boost recruitment efforts | 1 year after study initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Filgrastim, Pegfilgrastim