Correlation of Timing of Pegfilgrastim Administration and the Improvement of PIBP and PRO.

Study Overview
=================
Brief Summary
-----------------
Pegfilgrastim induced-bone pain is a common and important clinical problem. Currently, there is no effective solution. The bone pain it causes usually begins on the day of pegfilgrastim administration. Chemotherapy can also cause pain, which typically begins 24 to 48 hours after the completion of chemotherapy and lasts for 3 to 5 days. Regarding the timing of pegfilgrastim administration, the NCCN (National Comprehensive Cancer Network) guidelines suggest that 2 to 4 days after completing the chemotherapy is reasonable. In contrast, pegfilgrastim often be administrated 24 to 48 hours after finishing the chemotherapy in current clinical practice. Bone pain may be alleviated by delaying pegfilgrastim administration until 72 hours after the completion of chemotherapy to reduce the superimposed pain caused by chemotherapy and Pegfilgrastim.

Official Title
-----------------
Correlation of Timing of Pegfilgrastim Administration and the Improvement of PIBP(Paclitaxel Induced-bone Pain) and PRO (Patient-reported Outcomes).

Conditions
-----------------
Pegfilgrastim, Bone Pain, Chemotherapy, Breast Cancer, Patient-reported Outcomes

Intervention / Treatment
-----------------
* Other: Timing of pegfilgrastim administration


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater than or equal to 18 years and less than or equal to 70 years. Pathologically or histologically confirmed diagnosis of malignant breast tumor. Able to receive the scheduled chemotherapy regimen as scheduled and the chemotherapy regimen is an intermediate to high risk febrile neutropenia regimen. Able to fill out questionnaires independently Exclusion Criteria: Suffering from severe bone pain due to other diseases currently (defined as bone pain >5 points on a 0-10 Numerical Rating Scale due to non-breast malignancies and their related treatments). Allergy or contraindication to chemotherapeutic agents or pegfilgrastim. Previous use of pegfilgrastim. Pregnancy or lactation. Refused to sign the informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 24h group<br>Pegfilgrastim is administrated 24 hours after completing the chemotherapy in the 24-hour group. | Other: Timing of pegfilgrastim administration<br>* Timing of pegfilgrastim administration<br>|
| Other: 48h group<br>Pegfilgrastim is administrated 48hours after completing the chemotherapy in the 48-hour group. | Other: Timing of pegfilgrastim administration<br>* Timing of pegfilgrastim administration<br>|
| Other: 72h group<br>Pegfilgrastim is administrated 72 hours after completing the chemotherapy in the 72-hour group. | Other: Timing of pegfilgrastim administration<br>* Timing of pegfilgrastim administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the curve (AUC) for worst bone pain for days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration) in cycle 1. | Measured by Brief Pain Inventory-Short Form | Days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bone pain | Measured by Brief Pain Inventory-Short Form | Days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration). | 
| Incidence of severe bone pain | Measured by Brief Pain Inventory-Short Form | Days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration). | 
| Duration of bone pain | Measured by Brief Pain Inventory-Short Form | Days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration). | 
| Impact of bone pain on daily life and other aspects. | Measured by Brief Pain Inventory-Short Form | Days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration). | 
| Incidence of febrile neutropenia | Measured by thermometer and routine blood tests. | Monitor axillary temperature daily and do routine blood tests on the seventh day of each cycle. | 
| Leukocyte count | Measured routine blood tests. | Do routine blood tests on the seventh day of each cycle. | 
| Absolute neutrophil count | Measured routine blood tests. | Do routine blood tests on the seventh day of each cycle. | 
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score. | The EORTC QLQ-C30 is a questionnaire to assess quality of life (QoL), it is composed of 30 questions (items) resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, pain), and 6 single items (dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status indicate a better quality of life; a positive change from baseline indicates improvement. Lower scores on the symptom and single-item scales indicate a better quality of life; a negative change from baseline indicates improvement. | Before pegfilgrastim administration in the first chemotherapy cycle (baseline), day 7 after each cycle of pegfilgrastim administration. | 
| The area under the curve (AUC) for worst bone pain for days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration) in every cycle. | Measured by Brief Pain Inventory-Short Form | Days 1 through 8 (day 1 is defined as the day of pegfilgrastim administration). | 
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Breast Cancer-23 (EORTC QLQ-BR23) Score. | The EORTC QLQ-BR23 is a questionnaire to assess quality of life (QoL), it is composed of 23 questions (items) resulting in 4 functional scales (Body Image, Future Perspective, Sexual Functioning, Sexual Enjoyment) and 4 symptom scales (Systemic Therapy Side Effects, Upset by Hair Loss, Arm Symptoms, Breast Symptoms). All of the scales measures range in score from 0 to 100. Higher score for the functioning scales indicate a better quality of life; a positive change from baseline indicates improvement. Lower scores on the symptom scales indicate a better quality of life; a negative change from baseline indicates improvement. | Before pegfilgrastim administration in the first chemotherapy cycle (baseline), day 7 after each cycle of pegfilgrastim administration. | 
| Change From Baseline in European Quality of Life-Five Dimension-Five Level Scale (EQ-5D-5L) Score. | The EQ-5D-5L consists of a descriptive system that defines health in terms of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analog scale (VAS) for respondents to rate their current health status from 0 (worst health) to 100 (best imaginable health). A unique EQ-5D-5L health state (or profile) for each patient was generated by combining the results for the dimensions, consisting of a five-digit code. The health states were then converted to a preference-weighted summary score (weights derived from the general population), or EQ-5D-5L health utility index, with higher scores indicating better outcomes, and a positive change from baseline indicates improvement. | Before pegfilgrastim administration in the first chemotherapy cycle (baseline), day 7 after each cycle of pegfilgrastim administration. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pegfilgrastim, bone pain, patient-reported outcomes, chemotherapy, Breast Cancer