There are 6 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 ---
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 ---
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 ---
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 --- --- V600D ---
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 1The goal of this clinical research study is to learn if the combination of 2 drugs dabrafenib and trametinib can help to control melanoma that has or has not spread to the brain. The safety of this drug combination will also be studied. Dabrafenib is designed to block the mutated BRAF protein. This mutation is only found in moles of the skin and in melanoma cells. By blocking the protein, the drug may slow the growth of or kill cancer cells that have the protein. Trametinib is designed to block certain proteins that cause cancer cells to grow and multiply. This may cause the cancer cells to die.
3. BRAF mutation-positive melanoma (i.e., V600E, V600K or V600D) 4. For Cohort A, patients must have easily accessible tumor for a mandatory biopsy. --- V600E --- --- V600K --- --- V600D ---
Description: Overall response rate defined as percentage of subjects with a confirmed complete response (CR) or a partial response (PR) at any time as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Clinical responses will be evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks). Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): >20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of >5 mm; appearance of 1 or > new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.
Measure: Overall Response Rate (ORR) Time: Evaluation every 8 weeks (2 cycles) up to 12 monthsDescription: Clinical responses evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks). Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): >20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of >5 mm; appearance of 1 or > new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.
Measure: Number of Participants by Response Time: Evaluation every 8 weeks (2 cycles) up to 12 monthsDescription: Duration of response defined for subjects with a confirmed complete response (CR) or partial response (PR), as time from the first documented evidence of a CR or PR until the first documented disease progression or death due to any cause. Progression free survival (PFS) estimated and summarized using the method of Kaplan and Meier.
Measure: Progression-Free Survival (PFS) Time: Evaluation every 8 weeks (2 cycles) up to 12 monthsMEK113583 is a Phase II open-label, multi-site study to investigate the objective response rate, safety, and pharmacokinetics of GSK1120212 in subjects with BRAF mutation-positive melanoma who were previously treated with or without a BRAF inhibitor. GSK1120212 is a potent and highly selective inhibitor of MEK activation and kinase activity.
- Documented positive BRAF mutation (V600E, V600K, or V600D). --- V600E --- --- V600K --- --- V600D ---
Description: Best confirmed response was assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Best response was measured either as a complete response (CR), defined as the disappearance of all target lesions and pathological lymph nodes <10 millimeters (mm), or a partial response (PR), defined as at least a 30% decrease in the sum of the diameters of target lesions. To be assigned a status of confirmed CR or PR, a confirmatory disease assessment was required no less than 28 days after the criteria for response were first met.
Measure: Number of Participants With Best Confirmed Response Time: From Baseline (Day 1) until the time of the first documented evidence of a confirmed complete response or partial response (up to approximately 25 weeks)Description: The number of participants with best confirmed response was analyzed for the following subgroups of participants previously treated with standard therapy but not BRAF inhibitors: (1) participants with prior (before the start of this study) brain metastases (mets); (2) participants without prior brain mets; (3) participants with BRAF mutation V600E; (4) participants with BRAF mutation V600E and no prior brain mets; and (5) participants with BRAF mutation V600K. Objective response was assessed per RECIST version 1.1. Objective response was measured either as CR, defined as the disappearance of all target lesions and pathological lymph nodes <10 mm, or PR, defined as at least a 30% decrease in the sum of the diameters of target lesions. To be assigned a status of confirmed CR or PR, a confirmatory disease assessment was required no less than 28 days after the criteria for response were first met. Brain metastasis is a cancer that has spread to the brain from another location of the body.
Measure: Number of Participants With Best Confirmed Response in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors Time: From Baseline (Day 1) until the time of the first documented evidence of a confirmed CR or PR (up to approximately 25 weeks)Description: An interim analysis was performed using data collected approximately 12 and 13 weeks after the 30th participant was enrolled in the prior BRAF inhibitor and prior standard therapy groups, respectively. The best unconfirmed response by the investigator per RECIST version 1.1 was assessed. The study design permitted stopping the study for futility if <3 best confirmed responses were observed in the first 30 participants of each treatment arm after completing the first post-dose assessment at Week 8. Best response was measured as either a CR, defined as the disappearance of all target lesions and pathological lymph nodes <10 millimeters, or a PR, defined as at least a 30% decrease in the sum of the diameters of target lesions.
Measure: Number of Participants With Best Unconfirmed Response at the Time of the Interim Analysis (Week 8) Time: Week 8Description: Human plasma samples were analyzed for trametinib using a validated analytical method.
Measure: Mean Plasma Concentrations Time: Day 15, pre-dose, 0.5-2 hours (hrs) post-dose, 2-4 hrs post-dose, and 4-8 hrs post-dose; Week 4, pre-dose; Week 8, pre-dose; Week 12, pre-doseDescription: An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. AE and serious AE (SAE) data were collected from the start of the investigational product and continued until the End of Treatment Visit. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Measure: Number of Participants With Any Adverse Event (AE) Time: From the date of the first dose of study medication until 28 days after the last dose (up to 477 days)Description: Duration of tumor response is defined as the time from the first documented evidence of a CR or PR to disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause. No participants who were previously treated with BRAF inhibitors had a CR, defined as the disappearance of all target lesions and pathological lymph nodes <10 millimeters, or a PR, defined as at least a 30% decrease in the sum of the diameters of target lesions; thus, no duration of response data can be presented.
Measure: Duration of Tumor Response Time: From the time of the first documented evidence of a confirmed CR or PR until disease progression or death due to any cause (up to approximately 40 weeks)Description: PFS is defined as the interval between the treatment start date and the earliest date of disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause, whichever occurred first. Participants who had not progressed or died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Measure: Progression-free Survival (PFS) Time: Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)Description: PFS was analyzed for the following subgroups of participants previously treated with standard therapy but not BRAF inhibitors: (1) participants with prior (before the start of this study) brain metastases (mets); (2) participants without prior brain mets; (3) participants with BRAF mutation V600E; (4) participants with BRAF mutation V600E and no prior brain mets; and (5) participants with BRAF mutation V600K. Per RECIST version 1.1, PFS is defined as the interval between the treatment start date and the earliest date of disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause, whichever occurred earliest. Brain metastasis is a cancer that has spread to the brain from another location of the body.
Measure: PFS in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors Time: Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)Description: Overall survival is defined as the time from the treatment start date until death due to any cause. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Measure: Overall Survival Time: Baseline (Day 1) until death due to any cause (up to 134 weeks)Description: Overall survival (defined as the time from the treatment start date until death due to any cause) data data are presented as the number of participants who were alive 6 months, 12 months and 24 months after Baseline. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Measure: Number of Participants Who Survived Until 6 Months, 12 Months and 24 Months From Baseline Time: Month 6, Month 12 and Month 24Description: Tumor progression was assessed as disease progression (DP), defined as at least a 20 percent increase in the sum of diameters of target lesions (representative of all involved organs), taking as reference the smallest sum on study; unequivocal progression of non-target lesions; or the appearance of a new lesion. Because melanoma often progresses to the brain/central nervous system (CNS) and this study enrolled approximately 20% participants with prior brain metastases, tumor progression in the brain/CNS was summarized. Paticipants could have been included in more than one category.
Measure: Number of Participants With Tumor Progression Time: Baseline (Day 1) until tumor progression (up to approximately 57 weeks)