There are 2 clinical trials
This study aims to determine which of 3 drug combinations best reduces the size of tumour prior to surgery for advanced melanoma and prevents the recurrence of melanoma after surgery.
V600D, V600K, V600R, V600M). --- V600D --- --- V600K --- --- V600R --- --- V600M ---
Description: Proportion of patients with complete absence of residual melanoma cells in the planned resected tumour site(s) at week 6 surgery.
Measure: Pathological response rate Time: From baseline to 6 weeksDescription: Proportion of patients with complete and partial responses at 6 weeks compared to baseline per RECIST guidelines for each treatment arm.
Measure: Objective clinical (RECIST) response rate Time: From baseline to 6 weeksDescription: The amount of time that patients are disease free from the time of surgery at 6 weeks from study entry
Measure: Relapse free survival Time: 5 yearsDescription: The proportion of patients who are alive from the time of study entry
Measure: Overall survival Time: 5 yearsDescription: The number of patients (and the number of episodes) who develop a post operative infection of the surgical wound requiring intravenous antibiotics and/or wound drainage
Measure: Incidence of post operative infection Time: 6 weeksDescription: The number of patients (and the number of episodes) who develop a seroma at the surgical site that requires any intervention and the volume of seroma drainage
Measure: Incidence of post operative seroma formation Time: 6 weeksDescription: The number of days that a wound drain remains in situ from the time of surgery
Measure: Duration of post operative wound drainage time Time: 6 weeksDescription: The number of patients (and the number of episodes) who have a bleed from the post operative surgical wound that requires a blood transfusion or return to theatre to stop the bleeding
Measure: Incidence of post operative bleeding requiring return to theatre or transfusion Time: 6 weeksDescription: The change, if any, in the surgeon's assessment of 'operability' from baseline opinion (based on clinical and imaging examination) to time of operation
Measure: Comparison of surgeon's opinion of operability evaluated at baseline to time of surgery Time: Baseline and 6 weeksDescription: The number of study treatment related adverse events of all Common Terminology Criteria for Adverse Events (CTCAE) grades from the time of starting study treatment to the time of permanent discontinuation of study treatment
Measure: Incidence of any treatment-emergent adverse events Time: 52 weeksDescription: The effects of study treatment on the body's immune cells within the tumour tissue prior to surgery
Measure: Characterisation of the immunophenotype of tumour infiltrating cells in melanoma tissue Time: Baseline, Week 1, Week 2, Week 6Description: The effects of study treatment on the degree of necrosis and genetic markers in tumour tissue prior to surgery
Measure: Description of the morphological assessment of melanoma tissue Time: Baseline, Week 1, Week 2, Week 6Description: The effects of study treatment on the baseline function of RNA expression in tumour tissue prior to surgery
Measure: Description of the RNA expression profile of melanoma tumour Time: Baseline, Week 1, Week 2, Week 6Description: The effects of study treatment on the number and type of white cells in the blood
Measure: Measurement of leucocyte subpopulations in peripheral blood Time: Baseline, Week 1, Week 2, Week 6Description: The levels of melanoma DNA that is circulating in the blood stream and the changes during study treatment
Measure: Measurement of circulating tumour DNA Time: Baseline, Week 1, Week 2, Week 6Description: The activity of melanoma tissue assessed by the uptake of fludeoxyglucose (18F) in tumour cells viewed using positron emission tomography (PET) and how well this corresponds to the findings from the pathological examination of completely excised tumour tissue
Measure: Concordance of metabolic response measured by pathological response Time: 6 weeksDescription: The activity of melanoma tissue assessed by the uptake of fludeoxyglucose (18F) in tumour cells viewed using positron emission tomography (PET) and how well this corresponds to the assessment of tumour size and extent using computed tomography and magnetic resonance imaging scans
Measure: Concordance of metabolic response measured by RECIST response Time: 52 weeksDescription: he findings from the pathological examination of completely excised tumour tissue and how well this corresponds to the assessment of tumour size and extent using computed tomography and magnetic resonance imaging scans
Measure: Concordance of pathological response measured by RECIST response Time: 6 weeksDescription: The activity of recurrent melanoma tissue assessed by the uptake of fludeoxyglucose (18F) in tumour cells viewed using positron emission tomography (PET) and how well this corresponds to the assessment of tumour size and extent using computed tomography and magnetic resonance imaging scans
Measure: Concordance of metabolic response with RECIST response at relapse Time: 52 weeksDescription: The application of two different criterion to establish the tumour burden as assessed with computed tomorgraphy and magnetic resonanse imaging
Measure: Concordance of immune related response criteria (irRC) with RECIST response Time: Weeks 6 and 52Description: Characterisation of the bacterial diversity and composition in stool samples at baseline, prior to surgery at week 6, week 24 and at relapse.
Measure: Correlation of the gut microbiome with RECIST response to immunotherapy. Time: Baseline, Week 6, week 24, at relapse if this occurs within 5 years from study entryDescription: Diet plays a significant role in shaping the intestinal microbiome. Nutrition may influence the gut microbiome and response to immunotherapy.
Measure: Characterisation of self-reported dietary habits (including use of oral probiotics) and correlation with the gut microbiome. Time: BaselineThis is a single-centre, open-label Phase II study of the investigational drugs binimetinib and encorafenib that will be taken my mouth (orally) daily in adult patient with advanced and/or metastatic solid tumors for which no other standard therapy is available. The main purpose is to evaluate the objective response rate (ORR) of the study drugs in the growth of the cancer in patients with class 2 and 3 BRAF mutations.
6. Malignancy must express one of the following BRAF alterations: BRAF mutation affecting codon: 241, 257, 367, 462, 463, 464, 466, 467, 469, 485, 581, 586, 594, 595, 596, 597 598, 599, 601; V600 BRAF mutations: V600K (for any malignancy except melanoma), V600D, V600M, V600R; BRAF deletions ie. --- V600K --- --- V600D --- --- V600M ---