There are 5 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 ---
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 --- --- V600R ---
This is a screening study to detect BRAF V600 mutation-positive patients for enrollment into clinical research studies of Zelboraf (vemurafenib). Tumor samples will be collected and analyzed from eligible patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer) or multiple myeloma. All institutions with identified patients as defined by this screening protocol will have potential access to the separate vemurafenib protocol MO28072.
V600E, V600K, V600D, and V600R are the different types of BRAF V600 mutations.. Inclusion Criteria: - Histologically confirmed solid tumors (excluding melanoma and papillary thyroid cancer) or multiple myeloma refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate by the investigator - Patients with multiple myeloma must have received at least one line of prior systemic therapy for the treatment of multiple myeloma Exclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance status > 2 - Uncontrolled concurrent malignancy - Active or untreated CNS metastases - History of known carcinomatous meningitis - Prior treatment with a BRAF or MEK inhibitor (prior sorafenib is allowed) - Uncontrolled, severe medical illness or condition as defined in protocol MO28072 Inclusion Criteria: - Histologically confirmed solid tumors (excluding melanoma and papillary thyroid cancer) or multiple myeloma refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate by the investigator - Patients with multiple myeloma must have received at least one line of prior systemic therapy for the treatment of multiple myeloma Exclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance status > 2 - Uncontrolled concurrent malignancy - Active or untreated CNS metastases - History of known carcinomatous meningitis - Prior treatment with a BRAF or MEK inhibitor (prior sorafenib is allowed) - Uncontrolled, severe medical illness or condition as defined in protocol MO28072 Multiple Myeloma, Neoplasms Multiple Myeloma null --- V600E --- --- V600K --- --- V600D --- --- V600R ---
Description: Formalin-fixed paraffin-embedded (FFPEs) tumor samples (at least 5 serially-cut, unstained, 5 micrometer [μm] sections) were collected from eligible participants who consented to participate in the study. FFPE tumor samples were either from archived sections (from the initial diagnosis of cancer) or from fresh biopsies that were performed according to local standards. Tumor samples were then sent to a central laboratory to identify activating BRAF V600 mutations. Identification of mutations was done using bidirectional direct Sanger sequencing procedure.
Measure: Percentage of Participants With BRAF V600 Mutation Positivity in Tumor Samples by Cancer Type Time: Up to 1 yearDescription: FFPEs tumor samples (at least 5 serially-cut, unstained, 5 μm sections) were collected from eligible participants who consented to participate in the study. FFPE tumor samples were either from archived sections (from the initial diagnosis of cancer) or from fresh biopsies that were performed according to local standards. Tumor samples were then sent to a central laboratory to identify activating BRAF V600 mutations. Identification of mutations was done using bidirectional direct Sanger sequencing procedure. V600E, V600K, V600D, and V600R are the different types of BRAF V600 mutations.
Measure: Number of Participants Classified Based on Different Types of BRAF V600 Mutation Patterns in Tumor Samples Time: Up to 1 yearThis is a surgical biospecimen collection study. The purpose of this study is to understand how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn off the RAF signaling pathway. This is important because these drugs are currently FDA approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.
Allowable mutations include V600E, V600K, V600R, and V600D. --- V600E --- --- V600K --- --- V600R ---
Description: Obtain single time-point concentration of dabrafenib in enhancing brain tissue (ng/mL) using liquid chromatography/mass spectrometry with one single, random sample
Measure: Concentration of dabrafenib in brain tumor Time: Day 1Description: Obtain single time-point concentration of trametinib in enhancing brain tissue (ng/mL) using liquid chromatography/mass spectrometry with one single, random sample
Measure: Concentration of trametinib in brain tumor Time: Day 1This study will evaluate the safety and disease control rate of the combination of pembrolizumab plus low-dose interleukin-2 in patients who have either advanced melanoma or renal cell cancer.
If the melanoma expresses a BRAF mutation of V600E, V600K, or V600R patient must have received and progressed through a BRAF inhibitor or have failed that therapy due to toxicity. --- V600E --- --- V600K --- --- V600R ---
Description: Obtain preliminary data on the safety of LD-IL2 with pembrolizumab
Measure: Safety: adverse event profile Time: up to 90 days post-treatmentDescription: Estimate the disease control rate (CR+PR+SD by RECIST 1.1) among candidate patients with metastatic melanoma treated with pembrolizumab and LD-IL2 and to determine whether disease control is significantly improved. SD for 6 months or more will be considered SD for the purpose of this assessment.
Measure: Disease control rate: melanoma Time: baseline and every 9 weeks (up to week 104)Description: Estimate the disease control rate (CR+PR+SD by RECIST 1.1) among patients with metastatic renal cell cancer treated with pembrolizumab and LD-IL2 and to determine whether disease control is significantly improved. SD for 6 months or more will be considered SD for the purpose of this assessment.
Measure: Disease control rate: renal cell cancer Time: baseline and every 9 weeks (up to week 104)Description: Estimate progression-free survival defined as the duration of time from first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first
Measure: Progression free survival: metastatic melanoma Time: From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.Description: Estimate progression-free survival defined as the duration of time from first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first
Measure: Progression free survival: renal cell cancer Time: From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.