Phase II Study of ctDNA-guided Encorafenib Plus Cetuximab Retreatment in Patients BRAF V600E Mutated mCRC
NCT Number: NCT06578559
Acronym: BRICKET
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Colorectal Cancer
Interventions: DRUG: Cetuximab|DRUG: Encorafenib
Sponsor: Gruppo Oncologico del Nord-Ovest
Collaborators: Merck Sharp & Dohme LLC|Pierre Fabre Laboratories
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 16
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-23
Completion Date: 2027-04-01
Locations: Azienda Ospedaliero-Universitaria Pisana, Pisa, PI, 56126, Italy

Summary:
The aim of this study is to evaluate the activity, in terms of best response according to RECIST criteria 1.1 as assessed by the local investigator, of the ctDNA-guided retreatment with encorafenib plus cetuximab in BRAFV600E mutated mCRC patients experiencing benefit from previous exposure to encorafenib plus cetuximab (+/- chemotherapy) and with BRAFV600E mutated, KRAS, NRAS and MAP2K1 wild-type and MET not amplified status on ctDNA at the time of study entry.

Primary Outcome Measures: Objective Response Rate (ORR), The percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria. The determination of clinical response will be based on investigator-reported measurements.

Responses will be evaluated with a total body computed tomography (CT) scan every 8 weeks., 8 months after the enrollment of the last patient.
Secondary Outcome Measures: Progression Free Survival (PFS), The time interval computed from the date of study enrollment to the date of objective progression according to the RECIST criteria (version 1.1) or death, whatever comes first.

Patients alive and free of progression prior to the analysis cut-off date are censored at the date of the last disease assessment., 8 months after the enrollment of the last patient.|Overall Survival (OS), The time from the date of study enrollment to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive., 8 months after the enrollment of the last patient.|Overall Toxicity Rate, The percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (CTCAE version 5.0).

The CTCAE are classified as Grades 1 to 5 (from milder to more severe symptoms)., 8 months after the enrollment of the last patient.|Grade 3/4 Toxicity Rate, The percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (CTCAE version 5.0).

The CTCAE are classified as Grades 1 to 5 (from milder to more severe symptoms)., 8 months after the enrollment of the last patient.|Early Objective Response Rate (EORR), The percentage of patients, relative to the total of the enrolled subjects, achieving at least a 20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline., 8 months after the enrollment of the last patient.|Depth of Response (DpR), The relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline., 8 months after the enrollment of the last patient.|Objective Response Rate in the screening failure population (ORR-failure), Best objective response according to RECIST 1.1 criteria of the first line after ctDNA screening failure, if administered., 8 months after the enrollment of the last patient.|Progression Free Survival in the screening failure population (PFS-failure), The time interval computed from the start of the first treatment after ctDNA screening failure, if delivered, to the date of objective progression according to the RECIST criteria (version 1.1) or death, whichever comes first., 8 months after the enrollment of the last patient.|Overall Survival in the screening failure population (OS-failure), The time interval computed from the start of the first treatment after ctDNA screening failure, if delivered, to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive., 8 months after the enrollment of the last patient.|Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)., The EORTC QLQ-C30 contains functional scales, symptom scales, single items scale and a global health status/QoL scale. Raw scores are standardized and converted into scale scores ranging from 0 to 100.

Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.

Quality of life will be evaluated for patients who will have completed at least one questionnaire item at baseline and during the study period through descriptive summary statistics., Questionnaires will be administered at baseline (cycle 1 day 1), every 8 weeks thereafter, at disease progression and after 30 days following end of study treatment.|Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Module for Colorectal cancer 29 (EORTC QLQ-CR29)., The EORTC QLQ-CR29 includes 29 items that evaluate symptoms (gastrointestinal, urinary, pain and others) and functional areas (sexual, body image and others) that are associated with CRC and its treatments.

There are separate items for patients with and without a stoma and separate items to evaluate the sexual function of men and women. Raw scores are standardized and converted into scale scores ranging from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.

Quality of life will be evaluated for patients who will have completed at least one questionnaire item at baseline and during the study period through descriptive summary statistics., Questionnaires will be administered at baseline (cycle 1 day 1), every 8 weeks thereafter, at disease progression and after 30 days following end of study treatment.|Time To Deterioration in Quality of Life (TTD), The time from baseline to the first onset of a 10-point or greater decrease from study enrollment for functional scales or a 10-point or greater increase for symptom scales or death., 8 months after the enrollment of the last patient.