- ICH GCP
- US Clinical Trials Registry
- 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 (REaCT-OGF)
April 20, 2023 updated by: Ottawa Hospital Research Institute
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)
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.
Study Overview
Status
Recruiting
Conditions
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.
Study Type
Interventional
Enrollment (Anticipated)
240
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Lisa Vandermeer, MSc
- Phone Number: 70170 613-737-7700
- Email: lvandermeer@ohri.ca
Study Locations
-
-
Ontario
-
Ottawa, Ontario, Canada
- Recruiting
- The Ottawa Hospital Cancer Centre
-
Contact:
- Lisa Vandermeer, MSc
- Phone Number: 70170 613-737-7700
- Email: lvandermeer@ohri.ca
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Receive G-CSF
Receive G-CSF injections (either filgrastim or pegfilgrastim) after each cycle of paclitaxel chemotherapy.
|
Participants will receive G-CSF injection (either filgrastim or pegfilgrastim) after each paclitaxel cycle of DD-AC/T chemotherapy.
Other Names:
|
Experimental: Omission of G-CSF
Omission of G-CSF injections after each cycle of paclitaxel chemotherapy.
|
Participants will omit the use of G-CSF (either filgrastim or pegfilgrastim) after each paclitaxel cycle of DD-AC/T chemotherapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient-reported bone pain during cycle 1 of paclitaxel
Time Frame: 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).
|
At the end of cycle 1 of paclitaxel chemotherapy (each cycle is 14 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient-reported bone pain across all paclitaxel cycles
Time Frame: After each of the paclitaxel chemotherapy cycles (each cycle is 14 days)
|
Bone pain mean AUC across all cycles 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 all cycles 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).
|
After each of the paclitaxel chemotherapy cycles (each cycle is 14 days)
|
Peak bone pain experienced
Time Frame: Days 1 to 5 of the each of the paclitaxel chemotherapy cycles (each cycle is 14 days)
|
Peak bone pain experienced across all cycles of paclitaxel.
Measured by the patient reported daily pain score from days 1 to 5 during all 4 cycles of paclitaxel chemotherapy.
Bone pain is measured on a scale ranging from 0-10, 0 being no pain and 10 being the worst possible pain.
|
Days 1 to 5 of the each of the paclitaxel chemotherapy cycles (each cycle is 14 days)
|
Patient health-related quality of life
Time Frame: Through study completion, average of 12 weeks
|
Patient Health-Related Quality of Life (HR-QoL) based on the EuroQol 5 Dimension 5 Level (EQ-5D-5L) questionnaire.
|
Through study completion, average of 12 weeks
|
Rates of completion of 4 cycles of paclitaxel
Time Frame: Through study completion, average of 12 weeks
|
Rates of completion of 4 cycles of paclitaxel chemotherapy within 7 weeks (days 1 cycle 5 to day 1 cycle 8 of chemotherapy)
|
Through study completion, average of 12 weeks
|
Dose-intensity of paclitaxel chemotherapy
Time Frame: Through study completion, average of 12 weeks
|
Dose intensity of paclitaxel (mg/m2/wk) chemotherapy.
Dose intensity is a measure of a dose delay/dose reduction and premature chemotherapy discontinuation.
|
Through study completion, average of 12 weeks
|
Incidence of febrile neutropenia/neutropenia
Time Frame: Through study completion, average of 12 weeks
|
Incidences of febrile neutropenia/neutropenia will be collected using pretreatment bloodwork that is routinely performed before each chemotherapy cycle.
For this study, febrile neutropenia (FN) is defined as a one-time oral temperature greater or equal to 38.3 degrees Celsius (approximately 100.9 Fahrenheit) or a sustained temperature equal or greater than 38 degrees Celsius for 1 or more hours in a patient who has an absolute neutrophil count of less than 500 cells/microliter or an absolute neutrophil count expected to decrease to less than 500 cells/microliter within a 48-hour period.
|
Through study completion, average of 12 weeks
|
Incidence of treatment-related hospitalizations/ER visits
Time Frame: Through study completion, average of 12 weeks
|
The number of treatment-related hospitalizations and emergency room visits that occur from the start of paclitaxel chemotherapy to 1 month after the last paclitaxel chemotherapy cycle
|
Through study completion, average of 12 weeks
|
Healthcare resource utilization: Emergency Room Visits
Time Frame: Through study completion, average of 12 weeks
|
The number of emergency room visits that occur will be collected.
|
Through study completion, average of 12 weeks
|
Healthcare resource utilization: Planned and Unplanned Provider Visits
Time Frame: Through study completion, average of 12 weeks
|
The number of planned and unplanned provider clinic visits, including visits to stretcher bay will be collected.
|
Through study completion, average of 12 weeks
|
Healthcare resource utilization: Phone Calls and Emails
Time Frame: Through study completion, average of 12 weeks
|
The number of phone calls and emails to patient support line provider (reported by the patient) will be collected.
|
Through study completion, average of 12 weeks
|
Cost-effectiveness ratios
Time Frame: Through study completion, average of 12 weeks
|
There will be a cost-utility analysis comparing the differences in cost and quality-adjusted life years (QALY) between omitting G-CSF and standard G-CSF use.
The statistical analysis will be conducted in accordance with current guidelines for clinical and cost-effectiveness analysis alongside randomized clinical trials (RCTs).
Health utility values will be derived from EQ-5D-5L scores using the published mapping algorithm.
|
Through study completion, average of 12 weeks
|
Incidence of chemotherapy-related mortality
Time Frame: Through study completion, average of 12 weeks
|
Deaths from start of chemotherapy to one month after completion of last chemotherapy cycle
|
Through study completion, average of 12 weeks
|
Rate of secondary G-CSF or antibiotic use
Time Frame: Through study completion, average of 12 weeks
|
Rates of added G-CSF use for both randomization arms will be collected.
As well as the addition of antibiotic use.
|
Through study completion, average of 12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Xinni Song, MD, Ottawa Hospital Research Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 17, 2023
Primary Completion (Anticipated)
October 1, 2025
Study Completion (Anticipated)
October 1, 2025
Study Registration Dates
First Submitted
January 24, 2023
First Submitted That Met QC Criteria
February 22, 2023
First Posted (Actual)
March 3, 2023
Study Record Updates
Last Update Posted (Actual)
April 24, 2023
Last Update Submitted That Met QC Criteria
April 20, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- REaCT-OGF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Early-stage Breast Cancer
-
Dana-Farber Cancer InstituteCompletedEarly Stage Breast Cancer | Breast Cancer Stage I | Breast Cancer Stage IIUnited States
-
Jonsson Comprehensive Cancer CenterDaiichi Sankyo Co., Ltd.; Translational Research in Oncology-U.SRecruitingInvasive Breast Cancer | Stage II Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Hormone Receptor Positive Breast Carcinoma | Early-stage Breast Cancer | Stage III Breast CancerUnited States
-
Tanvex BioPharma USA, Inc.CompletedBreast Cancer | Breast Neoplasms | HER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Early-stage Breast CancerBelarus, Chile, Georgia, Hungary, India, Mexico, Peru, Philippines, Russian Federation, Ukraine
-
Stanford UniversityTerminatedBreast Cancer | Breast Cancer Early Stage Breast Cancer (Stage 1-3) | Breast Cancer Metastatic Breast CancerUnited States
-
Stanford UniversityNational Institutes of Health (NIH); University of California; Breast Cancer... and other collaboratorsActive, not recruitingBreast Cancer | Breast Cancer Non-invasive Breast Cancer | Breast Cancer Early Stage Breast Cancer (Stage 1-3)United States
-
University of Wisconsin, MadisonRecruitingEarly-stage Breast CancerUnited States
-
Shandong Cancer Hospital and InstituteRecruitingEarly-stage Breast Cancer | Breast Conserving SurgeryChina
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); National Institutes of Health (NIH)Active, not recruitingStage 0 Breast Cancer | Cancer Survivor | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Early-Stage Breast Carcinoma | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
MedStar Franklin Square Medical CenterMedstar Health Research InstituteActive, not recruitingEarly Stage Breast CancerUnited States
-
Fudan UniversityHuazhong University of Science and Technology; LinkDoc Technology (Beijing)...RecruitingEarly-stage Breast CancerChina
Clinical Trials on Granulocyte Colony-Stimulating Factor (G-CSF)
-
Catholic University of the Sacred HeartWithdrawn
-
University Hospital MuensterCompletedAmyotrophic Lateral Sclerosis | Chronic StrokeGermany
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingBreast Ductal Carcinoma In SituUnited States
-
Hospital Sao RafaelCompletedChronic Chagasic MyocarditisBrazil
-
TECAM GroupHospital General Universitario Gregorio MarañonUnknownReperfused Acute Myocardial InfarctionSpain
-
University of Mississippi Medical CenterUnknownPediatric Cancer | Chemotherapy-Induced Febrile Neutropenia | Chemotherapy-induced Neutropenia | Granulocyte Colony-Stimulating FactorUnited States
-
Xiamen Amoytop Biotech Co., Ltd.Shanghai Jiao Tong University Affiliated First People's HospitalCompleted
-
Serhat Gumrukcu, MD PhDFrida Therapeutics LLCRecruiting
-
Lei LiRecruitingFebrile Neutropenia | Epithelial Ovarian Cancer | Adverse Event | Cost-effectiveness | Myelosuppression Adult | Colony Stimulating FactorsChina
-
Centre Georges Francois LeclercCompleted