2023-509088-26-00
Recruiting
Phase 2
Single arm phase II study of ctDNA-guided encorafenib plus cetuximab retreatment in patients with BRAF V600E mutated mCRC. BRICKET study
Gruppo Oncologico Del Nord Ovest17 sites in 1 country16 target enrollmentStarted: June 21, 2024Last updated:
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 16
- Locations
- 17
- Primary Endpoint
- Objective Response Rate (ORR) defined as 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 chest and abdominal computed tomography (CT) scan every 8 weeks.
Overview
Brief Summary
The primary objective 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 BRAF and EGFR blockade (+/- chemotherapy) and with BRAFV600E mutated, KRAS, NRAS and MAP2K1 wild-type and MET not amplified status on ctDNA at the time of study entry.
Study Design
- Allocation
- Not Applicable
- Primary Purpose
- Interventional Phase
- Masking
- None
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Histologically proven diagnosis of colorectal adenocarcinoma
- •Previous treatment with immune checkpoint inhibitors (anti-PD-1/PD-L1 alone or in combination with anti-CTLA-4 agent), in the case of MSI-H or dMMR mCRC
- •Availability of blood sample for ctDNA analysis within 28 days prior enrolment
- •BRAFV600E mutated status of ctDNA at screening (central laboratory assessment by means of GUARDANT360 CDx, Guardant Health)
- •KRAS, NRAS, MAP2K1 wild-type status and MET not amplified status in ctDNA at screening (central laboratory assessment by means of GUARDANT360 CDx, Guardant Health)
- •Availability of archival tumour tissue (primary tumour and/or metastases) for biomarker analysis
- •Neutrophils >1.5 x 109/L, Platelets >100 x 109/L, Hgb >9 g/dl. Transfusions will be permitted provided the patient has not received more than two units red blood cells in the prior 4 weeks to achieve this criterion
- •Adequate renal function characterised by serum creatinine ≤ 1.5 × upper limit of normal (ULN), or calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL/min at screening;
- •Adequate hepatic function characterised by the following at screening: Serum total bilirubin ≤ 1.5 × ULN and < 2 mg/dL. Note: Patients who have a total bilirubin level > 1.5 × ULN will be allowed if their indirect bilirubin level is ≤ 1.5 × ULN; Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases. In the presence of documented Gilbert’s syndrome, a value of total bilirubin < 3 × ULN is acceptable
- •Adequate electrolytes at baseline, defined as serum potassium and magnesium levels within institutional normal limits (Note: replacement treatment to achieve adequate electrolytes will be allowed)
Exclusion Criteria
- •Known hypersensitivity or contraindications to trial drugs or any component of the trial drugs
- •Discontinuation of previous treatment with encorafenib and/or cetuximab with or without chemotherapy due to encorafenib- and/or cetuximab-related adverse events
- •Symptomatic brain metastases or spinal cord compression. Notes: Patients previously treated or untreated for these conditions who are asymptomatic in the absence of corticosteroid and antiepileptic therapy are allowed. Brain metastases or spinal cord compression must be stable for ≥ 4 weeks, with imaging (e.g., magnetic resonance imaging [MRI] or computed tomography [CT]) demonstrating no current evidence of progressive brain metastases or spinal cord compression at screening
- •Leptomeningeal disease
- •Other co-existing malignancies or malignancies diagnosed within the last 5 years except for adequately treated localised basal and squamous cell carcinoma or cervical cancer in situ
- •Treatment with any investigational drug within 30 days prior to enrolment or two investigational agent half-lives (whichever is longer)
- •Impaired gastrointestinal function (i.e., uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, small bowel resection) or disease which may significantly alter the absorption of oral study intervention or recent changes in bowel function suggesting current or impending bowel obstruction
- •Use of any herbal medications/supplements or any medications or foods that are moderate or strong inhibitors or inducers of CYP3A4/5 ≤1 week prior to the start of treatment
- •Diagnosis of interstitial pneumonitis or pulmonary fibrosis
- •Known history of acute or chronic pancreatitis within 6 months prior to the start of the treatment
Outcomes
Primary Outcomes
Objective Response Rate (ORR) defined as 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 chest and abdominal computed tomography (CT) scan every 8 weeks.
Objective Response Rate (ORR) defined as 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 chest and abdominal computed tomography (CT) scan every 8 weeks.
Secondary Outcomes
- Progression Free Survival (PFS) is defined as 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.
- Overall survival (OS) is defined as 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.
- Overall Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0)
- G3/4 Toxicity Rate is defined as 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 (version 5.0)
- Early Objective Response Rate (EORR) is defined as the percentage of patients, relative to the total of the enrolled subjects, achieving a ≥20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline
- Depth of Response (DpR) is defined as 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
- Clinical outcomes of the screening failure population include collection of therapeutic choices after ctDNA screening; ORRfailure; PFSfailure of the first line after ctDNA screening; OSfailure. 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.
- Quality of Life (QoL) is assessed using the EORTC QLQ-C30 and the EORTC QLQ-CR29 questionnaires, will be evaluated from patients who have completed at least one questionnaire item at baseline and during the study period through descriptive summary statistics.
- Time To Deterioration in Quality of Life (TTD) is defined as 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.
Investigators
Laura Delliponti
Scientific
Gruppo Oncologico Del Nord Ovest
Study Sites (17)
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