Correlation of Timing of Pegfilgrastim Administration and PIBP.

Correlation of Timing of Pegfilgrastim Administration and PIBP(Pegfilgrastim-induced Bone Pain)

According to the National Comprehensive Cancer Network (NCCN) guidelines, patients receiving high-risk or moderate-risk febrile neutropenia (FN) chemotherapy with at least one risk factor should receive prophylactic granulocyte colony-stimulating factors (G-CSFs). However, pegfilgrastim-induced bone pain (PIBP) remains a common and significant clinical issue without a satisfactory solution. Studies have reported that the incidence rate of PIBP is 71.3%, with severe bone pain occurring in 27.0% of cases. Currently, the available data on PIBP treatment are limited to case reports, reviews, and small randomized controlled trials.

The NCCN guidelines recommend preventive oral non-steroidal anti-inflammatory drugs or antihistamines as the treatment for PIBP. However, even with these preventive measures, the incidence rate of PIBP remains high at 61.1%, with severe bone pain occurring in 19.2% of cases. Severe bone pain can significantly impact the patient's health-related quality of life (HRQol), leading to potential refusal of pegfilgrastim administration and subsequent dose reduction in effective chemotherapy. Ultimately, this may have negative implications for tumor cure rates and patient survival.

Based on previous literature, it appears that delaying the administration of pegfilgrastim may be associated with a lower incidence of PIBP. Therefore, our study aims to investigate the correlation between the timing of pegfilgrastim administration and the occurrence of PIBP.

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Breast Cancer; Chemotherapy; Bone Pain; Patient-reported Outcomes; Pegfilgrastim
• Intervention / Treatment: Other: Timing of pegfilgrastim administration

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kun Wang, professor; Phone Number: 13922118086; Email: gzwangkun@126.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)
      • Contact: Kun Wang, professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age greater than or equal to 18 years and less than or equal to 70 years.
2. Pathologically or histologically confirmed diagnosis of primary breast cancer.
3. Able to receive the chemotherapy regimen as scheduled.
4. Able to understand Chinese and fill out the study-related questionnaires independently.
5. Given written informed consent.
6. There is no need to use prescription or over-the-counter drugs regularly because of pre-existing chronic pain.

Exclusion Criteria:

1. Suffering from bone pain due to other diseases currently.
2. Allergy or contraindication to chemotherapeutic agents or pegfilgrastim.
3. Previous use of pegfilgrastim.
4. Previous received chemotherapy.
5. Pregnancy or breastfeeding.
6. Concurrently accompanied by other primary malignant tumors.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

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 5 (day 1 is defined as the day of pegfilgrastim administration) in cycle 1.	Measured by Brief Pain Inventory-Short Form	Days 1 through 5 (day 1 is defined as the day of pegfilgrastim administration).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
Incidence of bone pain	Measured by Brief Pain Inventory-Short Form	Days 1 through 5 (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 5 (day 1 is defined as the day of pegfilgrastim administration).
Duration of bone pain and severe bone pain	Measured by Brief Pain Inventory-Short Form	Days 1 through 5 (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 5 (day 1 is defined as the day of pegfilgrastim administration).
Incidence of febrile neutropenia	Measured by thermometer and routine blood tests.	Patients monitor their axillary temperature daily and do routine blood tests on the seventh day of each cycle.
Leukocyte count	Measured by routine blood tests.	Patients do routine blood tests on the seventh day of each cycle.
Absolute neutrophil count	Measured by routine blood tests.	Patients do routine blood tests on the seventh day of each cycle.
The area under the curve (AUC) for worst bone pain for days 1 through 5 (day 1 is defined as the day of pegfilgrastim administration) in every cycle.	Measured by Brief Pain Inventory-Short Form	Days 1 through 5 (day 1 is defined as the day of pegfilgrastim administration).
Analgesic use	According to the diary written by the patient about the use of the analgesic.	Days 1 through 5 (day 1 is defined as the day of pegfilgrastim administration).
Incidence of neutropenia	Measured by routine blood tests.	Patients do routine blood tests on the seventh day of each cycle.

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Principal Investigator: Kun Wang, professor, Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: April 21, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; chemotherapy; patient-reported outcomes; pegfilgrastim; bone pain; health related-quality of life
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: KY-Q-2022-474-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No