S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER)

Study Overview
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Brief Summary
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This randomized clinical trial studies prophylactic colony stimulating factor management in patients with breast, colorectal or non-small cell lung cancer receiving chemotherapy and with risk of developing febrile neutropenia. Patients receiving chemotherapy may develop febrile neutropenia. Febrile neutropenia is a condition that involves fever and a low number of neutrophils (a type of white blood cell) in the blood. Febrile neutropenia increases the risk of infection. Colony stimulating factors are medications sometimes given to patients receiving chemotherapy to prevent febrile neutropenia. Colony stimulating factors are given to patients based on guidelines. Some clinics have an automated system that helps doctors decide when to prescribe them when there is a high risk of developing febrile neutropenia. Gathering information about the use of an automated system to prescribe prophylactic colony stimulating factor may help doctors use colony stimulating factor when it is needed.

Detailed Description
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PRIMARY OBJECTIVES: I. To compare the use of primary prophylactic colony stimulating factor (PP-CSF) according to recommended clinical practice guidelines among patients registered at intervention components versus usual care components. II. To compare the rate of febrile neutropenia (FN) among patients registered at intervention components versus usual care components. III. To compare the rate of FN among intermediate risk patients registered at intervention components by component treatment assignment (administer PP-CSF to intermediate risk patients versus not). SECONDARY OBJECTIVES: I. To compare the rate of FN among low-risk patients registered at intervention components versus usual care components. II. To compare the FN-related health-related quality of life (HRQOL) among low-risk patients registered at intervention components versus usual care components. III. To compare patient adherence to PP-CSF prescribing among patients registered at intervention components versus usual care components. IV. To compare patient knowledge of the indications for, efficacy of, and side effects associated with PP-CSF between the initiation and conclusion of the first cycle of myelosuppressive systemic therapy among patients registered at intervention components versus usual care components. V. To compare the proportion of patients completing the initial systemic therapy regimen at planned duration and at planned dose intensity among patients registered at intervention components versus usual care components. VI. To compare antibiotic use both as prophylaxis and as treatment for FN among patients registered at intervention components versus usual care components. VII. To compare the rate of FN-related emergency department visits and hospitalizations among intermediate risk patients registered to Intervention components by component treatment assignment (administer PP-CSF to intermediate risk patients versus not). VIII. To compare the FN-related health-related quality of life (HRQOL) among intermediate risk patients registered to intervention components by component treatment assignment (administer PP-CSF to intermediate risk patients versus not). IX. To compare overall survival among intermediate risk patients registered to intervention components by component treatment assignment (administer PP-CSF to intermediate risk patients versus not). TERTIARY OBJECTIVES: I. To characterize and descriptively report the differences among cohort components and the intervention and usual care components. II. To evaluate the time to invasive recurrence in non-metastatic patients by component treatment assignment OUTLINE: Patients are randomized to 1 of 4 clinic groups. CLINIC GROUP 1 (CLINIC WITH AUTOMATED SYSTEM): Patients with a high risk of developing FN receive CSF based on the automated system recommendations. The automated system suggests that CSFs not be used for drugs that have a low risk of FN. CLINIC GROUP 2 (CLINIC WITH NO AUTOMATED SYSTEM): Patients receive CSF based on clinical practice guidelines. CLINIC GROUP 3 (CLINIC WITH AUTOMATED SYSTEM): Patients with a high or moderate risk of developing FN receive CSF based on the automated system recommendations. The automated system suggests that CSFs not be used for drugs that have a low risk of FN. CLINIC GROUP 4 (CLINIC WITH AUTOMATED SYSTEM): Patients with a high risk of developing FN receive CSF based on the automated system recommendations. The automated system suggests that CSF not be used for drugs that have a moderate risk of FN. After completion of study treatment, patients are followed up for 12 months.

Official Title
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A Pragmatic Trial to Evaluate a Guideline-Based Colony Stimulating Factor Standing Order Intervention and to Determine the Effectiveness of Colony Stimulating Factor Use as a Prophylaxis for Patients Receiving Chemotherapy With Intermediate Risk for Febrile Neutropenia - Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER)

Conditions
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Febrile Neutropenia, Stage 0 Breast Cancer, Stage 0 Colorectal Cancer, Stage 0 Non-Small Cell Lung Cancer, Stage I Colorectal Cancer, Stage IA Breast Cancer, Stage IA Non-Small Cell Lung Carcinoma, Stage IB Breast Cancer, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Breast Cancer, Stage IIA Colorectal Cancer, Stage IIA Non-Small Cell Lung Carcinoma, Stage IIB Breast Cancer, Stage IIB Colorectal Cancer, Stage IIB Non-Small Cell Lung Carcinoma, Stage IIC Colorectal Cancer, Stage IIIA Breast Cancer, Stage IIIA Colorectal Cancer, Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Breast Cancer, Stage IIIB Colorectal Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage IIIC Breast Cancer, Stage IIIC Colorectal Cancer, Stage IV Breast Cancer, Stage IV Non-Small Cell Lung Cancer, Stage IVA Colorectal Cancer, Stage IVB Colorectal Cancer

Intervention / Treatment
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* Other: Preventive Intervention
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a current diagnosis of breast cancer, non-small cell lung cancer, or colorectal cancer; the current diagnosis may be an initial diagnosis or recurrence and/or progression of previously diagnosed disease; cancer may be metastatic or non-metastatic Patients must be registered prior to or on the same day as their first cycle of chemotherapy for their current disease and stage 9or disease setting). Patients must not have had any systemic therapy (chemotherapy or combination regimens) in the 180 days just prior to registration. Prior biologic therapy, immunotherapy, tyrosine kinase inhibitors, and hormonal therapy are allowed. Patients must be planning to receive one of the study-allowed regimens as their initial treatment for their current disease; myelosuppressive therapy must follow the standard regimen, although a dose reduction of up to 10% is permitted. This treatment may be neoadjuvant or adjuvant chemotherapy. Patients must not be receiving or planning to receive concurrent radiation during systemic treatment. Patients must not have any known contraindication to CSFs prior to registration, including prior hypersensitivity to Escherichia coli-derived proteins, filgrastim, pegfilgrastim, or tbo-filgrastim Patients must be able to understand and provide information for the patient-completed study forms in either English or Spanish Patients may have had a prior malignancy Patients must not be participating or plan to participate in other clinical trials that involve investigational systemic cancer treatments or investigational uses of CSF during their first 6 months after registration Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clinic group 1 (clinics with existing automated system for CSF prescribing)<br>CSF prescribing for patients taking anti-cancer drugs is based on existing automated system recommendations: CSF is recommended for drugs with high risk of FN; CSF is not recommended for drugs with low risk of FN. | Other: Preventive Intervention<br>* Automated ordering system recommends prescribing or not prescribing CSF based on drug's risk level for FN<br>* Other names: PRYLX;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Clinic group 2 (clinics with no automated system for CSF prescribing)<br>CSF prescribing for patients taking anti-cancer drugs is based on existing clinical practice guidelines. | Other: Preventive Intervention<br>* Automated ordering system recommends prescribing or not prescribing CSF based on drug's risk level for FN<br>* Other names: PRYLX;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Clinic group 3 (clinics with automated system for CSF prescribing)<br>CSF prescribing for patients taking anti-cancer drugs is based on automated system recommendations: CSF is recommended for drugs with intermediate or high risk of FN; CSF is not recommended for drugs with low risk of FN. | Other: Preventive Intervention<br>* Automated ordering system recommends prescribing or not prescribing CSF based on drug's risk level for FN<br>* Other names: PRYLX;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Clinic group 4 (clinics with automated system for CSF prescribing)<br>CSF prescribing for patients taking anti-cancer drugs is based on automated system recommendations: CSF is recommended for drug with high risk of FN; CSF is not recommended for drugs with intermediate or low risk of FN. | Other: Preventive Intervention<br>* Automated ordering system recommends prescribing or not prescribing CSF based on drug's risk level for FN<br>* Other names: PRYLX;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With CSF Prescribed as Primary Prophylaxis | To compare the use of primary prophylactic colony stimulating factor (PP-CSF) according to recommended clinical practice guidelines among participants registered at intervention components versus usual care components. Primary prophylaxis of CSF (PP-CSF) is defined as the initiation of granulocyte CSFs during the first cycle of myelosuppressive systemic therapy, given 24 to 72 hours after cessation of systemic therapy. Separate mixed effects logistic models will be fit to assess the effect of the intervention on PP-CSF use. The rate of CSF prescribing is defined as the percent of participants prescribed CSF as primary prophylaxis out of the total number of participants within each arm. | Baseline to up to 14 days | 
| Incidence of Febrile Neutropenia | To compare the rate of febrile neutropenia (FN) among participants, at any risk level, registered at intervention components versus usual care components. Febrile neutropenia is defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) as an absolute neutrophil count (ANC) < 1000/µL and a single temperature of > 38.3°C (101°F) or a sustained temperature of ≥ 38°C (101°F) for more than one hour. | Within 6 months post registration | 
| Incidence of Febrile Neutropenia Among Intermediate Risk Participants | To compare the rate of FN among intermediate risk participants registered at intervention components by component treatment assignment (administer PP-CSF to intermediate risk participants versus not). Febrile neutropenia is defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) as an absolute neutrophil count (ANC) < 1000/µL and a single temperature of > 38.3°C (101°F) or a sustained temperature of ≥ 38°C (101°F) for more than one hour. | Within 6 months post registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Febrile Neutropenia Among Low Risk Participants | To compare the rate of FN among low-risk participants registered at intervention components versus usual care components. Febrile neutropenia is defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) as an absolute neutrophil count (ANC) < 1000/µL and a single temperature of > 38.3°C (101°F) or a sustained temperature of ≥ 38°C (101°F) for more than one hour. | Within 6 months of registration | 
| FN-related Health-Related Quality of Life (HRQOL) Among Low Risk Participants | To compare the FN-related health-related quality of life (HRQOL) among low-risk participants registered at intervention components versus usual care components. Assessed using the Functional Assessment of Cancer Therapy - Febrile Neutropenia (Version 4) (FACT-N). Includes FACT general cancer score and FN-related score. A linear mixed effects model will be fit to assess the effect of the intervention on HRQOL. Component-level characteristics, patient-level clinical and demographic variables will be adjusted. | Baseline to up to 14 days | 
| Participant Adherence Rates to PP-CSF Prescription | To compare adherence to PP-CSF prescribing among participants registered at intervention components versus usual care components. Participant adherence rates are obtained from the proportion receiving PP-CSF among those for whom PP-CSF was ordered by the physician. The primary adherence measure will be obtained from the participant's chart; secondary adherence will be measured via self-report on the Follow-Up Participant Survey. For the home and clinic settings, separate mixed effects logistic models will be used to assess the effect of the intervention on adherence to PP-CSF orders, treating adherence after the start of the study. Component-level characteristics, participant-level clinical and demographic variables will be adjusted. | Within 14 days after the completion of first course of therapy | 
| Change in Participant Knowledge of PP-CSF Indications | To compare participant knowledge of the indications for, efficacy of, and side effects associated with PP-CSF between the initiation and conclusion of the first cycle of myelosuppressive systemic therapy among participants registered at intervention components versus usual care components. Linear mixed effects model with a time variable and an interaction between randomized group and time will be used to analyze change in the patient knowledge score. Random effects will be used to accommodate both the correlation among measures from the same patient as well as the correlation among patients from the same component. Component-level characteristics, participant-level clinical and demographic variables will be adjusted. | Baseline to up to 14 days | 
| Proportion Completing Initial Systemic Therapy Regimen: a) at Planned Duration and b) at Planned Dose Intensity (Clinical) | To compare the proportion of participants completing the initial systemic therapy regimen at planned duration and at planned dose intensity among participants registered at intervention components versus usual care components.Two separate mixed effects logistic models will be used to assess the effect of the intervention on completion of the initial systemic therapy regimen (i) at planned duration and (ii) at planned dose intensity. Component-level characteristics, patient-level clinical and demographic variables will be adjusted. | Up to 12 months | 
| Prophylactic and FN-Related Antibiotic Use | To compare antibiotic use both as prophylaxis and as treatment for FN among participants registered at intervention components versus usual care components. Prophylactic and FN-related antibiotic use will be measured as total number of antibiotic agents used and duration of antibiotic use. A linear mixed effects model will be fit to assess the effect of the intervention on duration of antibiotics use with number of days. Mixed effects Poisson models will be used to assess the effect of the intervention on total number of antibiotics agents used. Three separate models will be fit, with the following outcomes: (i) the number of times antibiotics were used as prophylaxis, (ii) the number of times antibiotics were used as treatment for FN, and (iii) t | Within 30 days of therapy | 
| Rate of FN-Related Emergency Department Visits and Hospitalizations | To compare the rate of FN-related emergency department (ED) visits and hospitalizations among intermediate risk participants registered to intervention components by component treatment assignment (administer PP-CSF to intermediate risk participants versus not). FN-related ED visits and hospitalizations are defined as admission to ED or hospital with documentation of fever and decreased ANC. A mixed effects Poisson model will be used to assess the effect of the intervention on FN-related ED visits and hospitalizations. Robust variance estimation will be used to relax the strong assumptions about the variance made by Poisson regression. If a large number of zero counts is observed, then zero-inflated Poisson regression will be used. | At 6 months | 
| FN-related Health-Related Quality of Life (HRQOL) Among Intermediate Risk Participants | To compare the FN-related health-related quality of life (HRQOL) among intermediate risk participants registered to intervention components by component treatment assignment (administer PP-CSF to intermediate risk participants versus not). Assessed using the Functional Assessment of Cancer Therapy - Febrile Neutropenia (Version 4) (FACT-N). Includes FACT general cancer score and FN-related score. A linear mixed effects model will be fit to assess the effect of the intervention on HRQOL. Component-level characteristics, participant-level clinical and demographic variables will be adjusted. | Baseline to up to 14 days | 
| Overall Survival (OS) | To compare overall survival among intermediate risk participants registered to intervention components by component treatment assignment (administer PP-CSF to intermediate risk participants versus not). A Cox proportional hazards model will be used to model survival. Component-level characteristics, participant-level clinical and demographic variables will be adjusted. A separate analysis of cause-specific survival to address FN-related deaths will also be conducted. | Time from date of registration to date of death due to any cause, assessed up to 12 months |