Rechallenge of BRAF +/- MEK Inhibitors Following an Adverse Event in Patients With Cancer (BRAFREC)
October 13, 2021 updated by: University Hospital, Caen
Rechallenge of Rapidly Accelerated Fibrosarcoma B-type (BRAF) +/- Mitogen-activated Extracellular Signal-regulated Kinase (MEK) Inhibitors Following an Adverse Event in Patients With Cancer
Very little data are published on the safety of a rechallenge with a BRAF inhibitor or combination of BRAF and MEK inhibitor (BRAFi and MEKi) after an adverse event (AE).
This study aimed at identifying the recurrence rate of the same AE after a BRAFi +/- MEKi rechallenge in patients with cancer and the factors associated to the recurrence.
Study Overview
Detailed Description
This is an observational, cross-sectional, pharmacovigilance cohort study.
AEs were extracted from safety reports from the World Health Organization database VigiBase®, to evaluate the safety of a rechallenge with a BRAF inhibitor or combination of BRAF and MEK inhibitor (BRAFi and MEKi) after an adverse event (AE) in patients with cancer.
Study Type
Observational
Enrollment (Anticipated)
16000
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
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
N/A
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
The study population is made of individual case safety reports from the World Health Organization pharmacovigilance database VigiBase, where patients had an adverse event following BRAF+/-MEKi therapy intakes.
Description
Inclusion Criteria:
- All consecutive AE cases associated with BRAFi and MEKi therapy. Combination therapy cases, where BRAFi were concurrently reported with MEKi will be identified, as well as the combination therapy regimen (V+C, D+T, E+B). We will not study MEKi monotherapy cases
Exclusion Criteria:
- MEKi monotherapy cases
- Cases concurrently reporting on immune checkpoint inhibitor therapies
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
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Reports of adverse events associated with the use of BRAF +/- MEK inhibitors
Reports of adverse event (individual case safety reports) from Vigibase, the World Health Organization pharmacovigilance database related to the use of BRAF +/- MEK inhibitors from inception (1986) until March, 1, 2021 will be extracted. Cases concurrently reporting on immune checkpoint inhibitor therapies will be excluded. |
Reports of adverse events occurring in patients treated with at least one BRAFi or MEKi as reported in the individual case safety reports.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Recurrence rate
Time Frame: Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years
|
The primary outcome is the rate of recurrence of the same AE after a BRAFi+/- MEKi rechallenge among informative rechallenges The recurrence rate will be obtained by dividing the number of cases with an AE recurrence by the number of informative rechallenges and will be expressed as a percentage
|
Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Comparison of rechallenge and non-rechallenge cases
Time Frame: Up to 10 years
|
Baseline characteristics (initial adverse event, cancer indication, age, sex) Measurements are the Medical Dictionary for Regulatory Activities preferred terms for adverse events and cancer indications, the Anatomical and Therapeutical Class for drugs.
Age is categorized (18-45, 45-64, 65-74, > 75y.o.), sex (male, female).
|
Up to 10 years
|
|
Factors associated with the recurrence after a rechallenge among informative rechallenges (i.e. variables associated with a higher recurrence rate, in a regression model)
Time Frame: Up to 10 years
|
Across baseline characteristics (initial adverse event, cancer indication, age, sex). Measurements are the Medical Dictionary for Regulatory Activities preferred terms for adverse events and cancer indications, the Anatomical and Therapeutical Class for drugs. Age is categorized (18-45, 45-64, 65-74, > 75y.o.), sex (male, female). The recurrence is defined as a second occurrence of an initial adverse event after the treatment was reintroduced. It is a dichotomous outcome. Data will be analyzed through a regression model, so as to determinate which of these covariates are associated with a higher recurrence rate. |
Up to 10 years
|
|
Rate of occurrence of a different AE after a monotherapy or combination therapy rechallenge (among informative rechallenges)
Time Frame: Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years
|
The occurrence rate will be obtained by dividing the number of cases with another AE that occurred following a treatment rechallenge by the number of informative rechallenges and will be expressed as a percentage
|
Up to the date of the individual case safety report notification in VigiBase(r), assessed up to 10 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Charles Dolladille, University Hospital, Caen
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)
January 1, 2011
Primary Completion (Actual)
March 1, 2021
Study Completion (Anticipated)
December 1, 2021
Study Registration Dates
First Submitted
April 28, 2021
First Submitted That Met QC Criteria
October 13, 2021
First Posted (Actual)
October 15, 2021
Study Record Updates
Last Update Posted (Actual)
October 15, 2021
Last Update Submitted That Met QC Criteria
October 13, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Other Study ID Numbers
- BRAFREC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
IPD Plan Description
Data for this study are available at http://www.vigiacess.org/.
Dissemination to study participants / researchers is not possible outside of the dedicated website.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
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.