Clinical trial NCT01813721: Study Investigating How Physicians Assess the Risk of Patients Developing Febrile Neutropenia During Chemotherapy.
Official title: Study to Investigate Which Clinical Risk Factors Are Considered by Physicians When Conducting Overall Febrile Neutropenia Risk Assessments for Patients Receiving Chemotherapy With an Intermediate (10% - 20%) Febrile Neutropenia Risk.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chemotherapy-induced Febrile Neutropenia
Keywords: NHL
Breast Cancer
Lung Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-03-19
Enrollment: 1007
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Eligible subjects will have NHL, breast or lung cancer and be due to initiate one of the permitted standard dose chemotherapy regimens listed in the protocol (those with a documented intermediate FN risk of 10-20%). Subjects will be prospectively and sequentially identified by approximately 150-200 investigators during their clinics distribututed in 11 countries.

Brief summary: This is a prospective observational study investigating how physicians assess the risk of febrile neutropenia (FN) developing in patients who will receive chemotherapy.

Approximately 150-200 investigators will take part in about 100 sites in Europe, Canada and Australia. Approximately 1000 subjects will be studied, all of whom will have non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), non-Hodgkin's lymphoma (NHL) or breast cancer and will be due to receive one of the specific chemotherapy regimens of interest.

Investigators' approach to FN risk assessment will be studied using lists of possible risk factors they may consider during their assessment. Investigators will be asked to select and rank the factors they consider the most important when assessing the overall FN risk of a subject and when making the decision whether to treat with granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (PP). They will be asked to make these selections based initially on their own routine clinical practise and subsequently relating specifically to each subject recruited.

This is a non-interventional study that involves no procedures outside normal care for the subjects; all data collection will be completed prior to chemotherapy administration.

Detailed description: Although a formal hypothesis will not be tested in this observational study, it is hypothesized that the clinical risk factors ranked as the most important when conducting FN risk assessments by investigators are aligned with international guidelines and published data. Also, that the investigator's decision to treat with G-CSF PP is influenced by clinical and non-clinical risk factors (such as distance from site, estimated subject compliance, and access to fully reimbursed G-CSF).

Study Design: Prior to identifying eligible subjects, Investigators will be registered and will record baseline information. During this Baseline Investigator Assessment investigators will be provided with two lists of risk factors. Investigators must rank selected risk factors that they consider to be the most important when assessing 1) overall FN risk (only scientific factors will be included), and 2) when deciding on whether G-CSF PP treatment will be used or not (this list will also contain non clinical factors). They will also record their own FN risk intervention threshold, which is the FN risk threshold score at which they would use G-CSF PP in their usual clinical practice.

Investigators will then prospectively and sequentially identify eligible subjects with NHL, breast or lung cancer who are due to initiate one of the permitted standard dose chemotherapy regimens listed in the protocol. The permitted chemotherapy regimens have an estimated intermediate FN risk (10%-20%) documented in published data and/or international guidelines.

For each enrolled subject, Investigators will complete a Subject Assessment prior to the start of their chemotherapy. They will be provided with the same two lists of risk factors as in the Baseline Assessment and asked to complete them based on each specific subject. Investigators must rank selected risk factors that they consider to be the most important when assessing 1) overall FN risk (only scientific factors will be included), and 2) when deciding on whether G-CSF PP treatment will be used or not. They will also document their final estimated FN risk score as a percentage based on the subject's medical history and standard of care (SOC) assessments (their routine practice for assessing this risk), and a decision as to whether G-CSF PP will be administered. Investigators will record which type of G-CSF they plan to use if one will be used.

End of Study for a subject will occur once these activities have been completed, and a prescription for the first cycle of chemotherapy has been written. The subject data collected will only be historical subject information and laboratory data from SOC assessments performed prior to beginning chemotherapy treatment. No data will be collected after the initiation of chemotherapy.

The approach to the statistical analysis will be generally descriptive in nature. The primary analysis will be conducted at two levels; investigator level and the subject level. It is expected that the opinions of investigators at a single site (that is, a department within a cancer treatment centre) will be correlated. Also, that the opinions about subjects from a single investigator will be more alike than subjects of other investigators; adjustments will be made in the analyses to account for this. Confidence intervals for the investigator level analysis and the subject level data will obtained from Multi-level Modelling (MLM) to allow for the expected intra-site and intra-investigator correlation of investigators within sites and subjects within investigator. In general, categorical data will be summarised by the number and percentage of subjects in each category. Continuous data will be summarised by mean, standard deviation, median, lower and upper quartiles, minimum and maximum values. Two-sided exact 95% confidence intervals (obtained using MLM) will be presented, where appropriate.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Any stage NHL, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), or breast cancer initiating a new chemotherapy course
* Scheduled to receive one of the permitted standard dose chemotherapy regimens with an estimated intermediate (10%-20%) FN risk according to published data or guidelines (planned dose modifications +/-10% are allowable).
* Before any study-specific procedure, the appropriate written informed consent must be obtained where this is required by local regulations

Exclusion Criteria:

* Ongoing or planned concurrent participation in any clinical study involving Investigational Product that has not been approved by the European Medicines Agency (EMA) or competent authority for any indication,
* Ongoing or planned concurrent participation in any clinical study where the administration of Colony Stimulating Factor (CSF) is determined by the protocol (clinical trials on an approved drug and observational trials are permitted as long as these do not mandate how neutropenia should be treated)
* Prior stem-cell transplantation (includes bone marrow transplantation)

Primary outcomes:
measure: Percentage of Investigators Who Ranked Age and Chemotherapy Regimen as a Risk Factor for Febrile Neutropenia
timeFrame: Baseline (prior to participant enrolment)
measure: Percentage of Investigators Who Ranked Each Factor as a Risk Factor for Febrile Neutropenia (FN)
timeFrame: Assessed at Baseline, prior to participant enrolment.
measure: Percentage of Participants for Whom Age and Chemotherapy Regimen Were Ranked as an Important Risk Factor
timeFrame: At enrolment, prior to chemotherapy initiation
measure: Percentage of Participants for Whom Each FN Risk Factor Was Ranked as Important
timeFrame: At enrolment, prior to chemotherapy initiation.
Secondary outcomes:
measure: Percentage of Investigators Who Ranked Each Factor in the Granulocyte Colony Stimulating Factor (G-CSF) Primary Prophylaxis (PP) Decision as Important
timeFrame: Assessed at baseline, prior to participant enrolment.
measure: Percentage of Investigators Who Ranked Each Factor in the G-CSF PP Decision as Important by Clinical Specialty
timeFrame: Assessed at baseline, prior to participant enrolment.
measure: Percentage of Investigators Who Ranked Each Factor in the G-CSF PP Decision as Important by Number of Years in Clinical Practice in Oncology / Hematology
timeFrame: Assessed at baseline, prior to participant enrolment.
measure: Percentage of Investigators Who Ranked Each Factor in the G-CSF PP Decision as Important by Institution Type
timeFrame: Assessed at baseline, prior to participant enrolment.
measure: Percentage of Participants for Whom Each Factor Was Ranked in the Granulocyte Colony Stimulating Factor (G-CSF) Primary Prophylaxis (PP) Decision as Important
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each Factor Was Ranked in the G-CSF PP Decision as Important by Country
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each Factor Was Ranked in the G-CSF PP Decision as Important by Clinical Specialty
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each Factor Was Ranked in the G-CSF PP Decision as Important by Number of Years in Clinical Practice in Oncology / Hematology
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each Factor Was Ranked in the G-CSF PP Decision as Important by Institution Type
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each Factor Was Ranked in the G-CSF PP Decision as Important by Tumor Type
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Investigators Who Ranked Each Factor as a Risk Factor for Febrile Neutropenia by Clinical Specialty
timeFrame: Assessed at Baseline, prior to participant enrolment.
measure: Percentage of Investigators Who Ranked Each Factor as a Risk Factor for Febrile Neutropenia by Number of Years in Clinical Practice in Oncology / Hematology
timeFrame: Assessed at Baseline, prior to participant enrolment.
measure: Percentage of Investigators Who Ranked Each Factor as a Risk Factor for Febrile Neutropenia by Institution Type
timeFrame: Assessed at Baseline, prior to participant enrolment.
measure: Percentage of Participants for Whom Each FN Risk Factor Was Ranked as Important by Country
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each FN Risk Factor Was Ranked as Important by Clinical Specialty
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each FN Risk Factor Was Ranked as Important by Number of Years in Clinical Practice in Oncology / Hematology
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each FN Risk Factor Was Ranked as Important by Institution Type
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants for Whom Each FN Risk Factor Was Ranked as Important by Tumor Type
timeFrame: At enrolment, prior to chemotherapy initiation.
measure: Percentage of Participants With an Investigator-assessed FN Risk at or Above the Investigator Self-reported FN-risk Intervention Threshold Who Were Planned to Receive G-CSF PP
timeFrame: At Baseline and at enrolment, prior to chemotherapy initiation.
Other outcomes:
Locations:
city: Tweed Heads
country: Australia
facility: Research Site
state: New South Wales
city: Bendigo
country: Australia
facility: Research Site
state: Victoria
city: Shepparton
country: Australia
facility: Research Site
state: Victoria
city: Wodonga
country: Australia
facility: Research Site
state: Victoria
city: Eggenburg
country: Austria
facility: Research Site
city: Graz
country: Austria
facility: Research Site
city: Leoben
country: Austria
facility: Research Site
city: Vöcklabruck
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Moncton
country: Canada
facility: Research Site
state: New Brunswick
city: Sault Ste. Marie
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Alès Cédex
country: France
facility: Research Site
city: Arras
country: France
facility: Research Site
city: Besançon Cedex
country: France
facility: Research Site
city: Brest Cedex 2
country: France
facility: Research Site
city: Créteil
country: France
facility: Research Site
city: Grenoble Cedex 9
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montluçon
country: France
facility: Research Site
city: Neuilly sur Seine
country: France
facility: Research Site
city: Nimes Cedex 2
country: France
facility: Research Site
city: Pierre Benite Cedex
country: France
facility: Research Site
city: Saint Quentin
country: France
facility: Research Site
city: Toulon Cedex
country: France
facility: Research Site
city: Villefranche Sur Saone Cedex
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Fulda
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Neustadt/Sachsen
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Stralsund
country: Germany
facility: Research Site
city: Twistringen
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Chania
country: Greece
facility: Research Site
city: Larissa
country: Greece
facility: Research Site
city: Nea Kifissia, Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Cork
country: Ireland
facility: Research Site
city: Galway
country: Ireland
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Foggia
country: Italy
facility: Research Site
city: Monza (MB)
country: Italy
facility: Research Site
city: Pordenone
country: Italy
facility: Research Site
city: Reggio Calabria
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Varese
country: Italy
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Elblag
country: Poland
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Braila
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Focsani
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Onesti
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Pitesti
country: Romania
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Huelva
country: Spain
facility: Research Site
state: Andalucía
city: Malaga
country: Spain
facility: Research Site
state: Andalucía
city: Zaragoza
country: Spain
facility: Research Site
state: Aragón
city: Palma de Mallorca
country: Spain
facility: Research Site
state: Baleares
city: La laguna
country: Spain
facility: Research Site
state: Canarias
city: Avila
country: Spain
facility: Research Site
state: Castilla León
city: Valladolid
country: Spain
facility: Research Site
state: Castilla León
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Pamplona
country: Spain
facility: Research Site
state: Navarra
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Freyer G, Kalinka-Warzocha E, Syrigos K, Marinca M, Tonini G, Ng SL, Wong ZW, Salar A, Steger G, Abdelsalam M, DeCosta L, Szabo Z. Attitudes of physicians toward assessing risk and using granulocyte colony-stimulating factor as primary prophylaxis in patients receiving chemotherapy associated with an intermediate risk of febrile neutropenia. Med Oncol. 2015 Oct;32(10):236. doi: 10.1007/s12032-015-0682-z. Epub 2015 Aug 28.
citation: Lyman GH, Dale DC, Legg JC, Abella E, Morrow PK, Whittaker S, Crawford J. Assessing patients' risk of febrile neutropenia: is there a correlation between physician-assessed risk and model-predicted risk? Cancer Med. 2015 Aug;4(8):1153-60. doi: 10.1002/cam4.454. Epub 2015 Mar 23.