Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03911869
Registration number
NCT03911869
Ethics application status
Date submitted
14/03/2019
Date registered
11/04/2019
Date last updated
31/05/2023
Titles & IDs
Public title
An Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-mutant Melanoma Brain Metastasis
Query!
Scientific title
A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis
Query!
Secondary ID [1]
0
0
C4221006
Query!
Secondary ID [2]
0
0
ARRAY-818-201
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
POLARIS
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Brain Metastases
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Malignant melanoma
Query!
Cancer
0
0
0
0
Query!
Brain
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - encorafenib
Treatment: Drugs - binimetinib
Experimental: Standard Dose Arm - Patients in the standard-dose treatment arm will receive encorafenib and binimetinib in 28-day cycles.
450 mg encorafenib orally once a day (QD)
45 mg binimetinib orally twice a day (BID)
Patients who are able to tolerate the standard dose during the first 4 weeks of treatment (Cycle 1) should be dose-escalated to 600 mg encorafenib QD plus 45 mg binimetinib BID provided they meet protocol-defined criteria.
Experimental: High Dose Arm - Patients in the high-dose treatment arm will receive encorafenib and binimetinib in 28-day cycles.
300 mg encorafenib orally twice a day (BID)
45 mg binimetinib orally twice a day (BID)
Treatment: Drugs: encorafenib
taken orally
Treatment: Drugs: binimetinib
taken orally
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Participants With Dose Limiting Toxicities (DLTs): Safety Lead-in (SLI) Phase
Query!
Assessment method [1]
0
0
DLT: any adverse event (AE) or laboratory abnormality not explained by underlying disease/disease progression/intercurrent illness/concomitant therapies/resulting in inability to tolerate 75% of planned dose of binimetinib or encorafenib during Cycle 1. Left ventricular ejection fraction (LVEF) >10%, Grade (G)>=3 cardiac disorders; G3/4 hypertension vascular disorders; G3/4 rash, hand foot skin reaction, photosensitivity; G3/4 diarrhea, nausea/vomiting Total bilirubin (TBL) G>=3 (>3.0*upper limit of normal [ULN)]);AST/ALT>5-8*ULN>5 days,>8*ULN,>3*ULN concurrent TBL>2*ULN;G>=3 serum creatinine, CK elevation, ECG QTcF prolonged,G3 troponin, electrolyte>72 hours,G3/4 amylase/lipase.G4 ANC, platelet count>7 days;G3/4 platelet count, other AE except lymphopenia. G>=3 retinopathy, other disorder>21 days; G2 uveitis/eye pain/blurred vision/decreased visual acuity; G4 other disorder; Other hematologic/non hematologic G>=3 AE. This outcome measure was planned to be analyzed in SLI phase only.
Query!
Timepoint [1]
0
0
Cycle 1 of SLI phase (up to 28 days)
Query!
Primary outcome [2]
0
0
Number of Participants With Treatment Emergent Adverse Events Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI _CTCAE) Version (v) 4.03: SLI Phase
Query!
Assessment method [2]
0
0
AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs: events between first dose of study drug up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state or start of subsequent anticancer drug therapy minus 1 day, whichever occurred first. Grades by NCI CTCAE v.4.03: Grade 1= asymptomatic or mild , clinical or diagnostic observations only, intervention not indicated; Grade 2= moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3= severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated; Grade 5= death related to AE. Number of participants with AEs per maximum grades were reported.
Query!
Timepoint [2]
0
0
Day 1 of dosing up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Query!
Primary outcome [3]
0
0
Number of Participants With Hepatology Laboratory Test Abnormalities: SLI Phase
Query!
Assessment method [3]
0
0
Hepatology laboratory abnormalities included following parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT or AST greater than or equal to (>=) 3*upper limit normal (ULN), >=5*ULN, >=10*ULN, >=20*ULN; total bilirubin (TBILI): >=2*ULN; ALT >=3*ULN and TBILI >=2*ULN; AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP >2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP <=2*ULN or missing. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [3]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Query!
Primary outcome [4]
0
0
Number of Participants With Shift From Baseline for Hematology and Coagulation Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: SLI Phase
Query!
Assessment method [4]
0
0
Hematology and coagulation laboratory test included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for hematology and coagulation laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [4]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Query!
Primary outcome [5]
0
0
Number of Participants With Shift From Baseline for Biochemistry Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: SLI Phase
Query!
Assessment method [5]
0
0
Biochemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine kinase (CK) increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, and serum amylase increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for biochemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [5]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Query!
Primary outcome [6]
0
0
Number of Participants With Notable Abnormal Vital Signs: SLI Phase
Query!
Assessment method [6]
0
0
Vital signs included: systolic and diastolic blood pressure (BP),pulse rate,weight and temperature.Systolic and diastolic BP was measured in millimeters of mercury (mmHg) based on criteria:High Systolic BP:>=160 mmHg and increase >=20 mmHg from baseline;High Diastolic BP:>=100 mmHg and increase>=15 mmHg from baseline;Low Systolic BP:<=90 mmHg with decrease from baseline of >=20 mmHg;Low Diastolic BP:<=50 mmHg with decrease from baseline of >=15 mmHg;Pulse rate was measured in beats per minute (bpm) based on criteria:High pulse rate >=120 bpm with increase from baseline of >=15 bpm;Low pulse rate <=50 bpm with decrease from baseline of >=15 bpm;Weight was measured in in kilogram (kg) based on criteria:Increase from baseline of >=10%,:>=20% decrease from baseline;Temperature was measured in degree Celsius (C) based on criteria:High body temperature >=37.5 degree C,Low body temperature <=36 degree C.Only those vital signs parameters in which at least 1 participant had data were reported.
Query!
Timepoint [6]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Query!
Primary outcome [7]
0
0
Number of Participants With Notable Abnormal Electrocardiogram (ECG) Values: SLI Phase
Query!
Assessment method [7]
0
0
In this outcome measure, number of participants with notable abnormal ECG values included: Fridericia's Correction Formula (QTcF) values in millisecond (msec) based on following criteria: 1) Increase from baseline >30 msec; 2) Increase from baseline >60 msec; 3) New >450 msec; 4) New >480 msec; and 5) New >500 msec; heart rate values in bpm based on following criteria: 1) Increase from baseline >25% and to a value >100; 2) Decrease from baseline >25% and to a value <50. Only those ECG parameters in which at least 1 participant had data were reported.
Query!
Timepoint [7]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Query!
Primary outcome [8]
0
0
Number of Participants With Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to AEs: SLI Phase
Query!
Assessment method [8]
0
0
An AE is any untoward medical occurrence in clinical investigation participant administered a product or medical device; event need not necessarily to have a causal relationship with treatment or usage. In this outcome measure, number of participants with incidence of dose interruptions, dose modifications and discontinuations due to AEs were reported.
Query!
Timepoint [8]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Query!
Primary outcome [9]
0
0
Brain Metastasis Response Rate (BMRR) Based on Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (mRECIST v1.1): Phase 2
Query!
Assessment method [9]
0
0
BMRR was reported in terms of percentage of participants who achieved a confirmed best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in brain metastasis per mRECIST v1.1 from date of first dose until disease progression, death due to any cause, or start of subsequent anticancer therapy, whichever occurred first. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Query!
Timepoint [9]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [1]
0
0
Extracranial Response Rate Based on RECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [1]
0
0
Extracranial response rate was defined as the percentage of participants with a BOR of confirmed CR or confirmed PR in extracranial lesions by investigator assessment per RECIST v1.1. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Query!
Timepoint [1]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [2]
0
0
Global Response Rate: SLI Phase and Phase 2
Query!
Assessment method [2]
0
0
Global response rate was defined as the percentage of participants with a BOR of confirmed CR or confirmed PR by investigator assessment in brain metastasis and extracranial lesions per combined mRECIST v1.1 and RECIST v1.1, respectively. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline).
Query!
Timepoint [2]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [3]
0
0
Disease Control Rate (DCR) for Brain Metastasis Response Based on mRECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [3]
0
0
DCR was defined as the percentage of participants with a BOR of CR, PR or stable disease (SD) by Investigator assessment per mRECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started.
Query!
Timepoint [3]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [4]
0
0
DCR for Extracranial Response Based on RECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [4]
0
0
DCR was defined as the percentage of participants with a BOR of CR, PR or SD by Investigator assessment per RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum demonstrates an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Query!
Timepoint [4]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [5]
0
0
DCR for Global Response: SLI Phase and Phase 2
Query!
Assessment method [5]
0
0
DCR was defined as the percentage of participants with a BOR of CR, PR or SD by Investigator assessment per RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must be <10 mm on the short axis. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline). SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to quality for PD. PD: at least a 20% increase in the sum of the diameters of target lesions, taking as a reference the smallest sum of diameters recorded since the treatment started (i.e., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of at least 5 mm.
Query!
Timepoint [5]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [6]
0
0
Duration of Response (DOR) for Brain Metastasis Response Based on mRECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [6]
0
0
DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.
Query!
Timepoint [6]
0
0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [7]
0
0
DOR for Global Response: SLI Phase and Phase 2
Query!
Assessment method [7]
0
0
DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. Any pathological lymph nodes must be <10 mm on the short axis. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline). DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.
Query!
Timepoint [7]
0
0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [8]
0
0
DOR for Extracranial Response Based on RECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [8]
0
0
DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.
Query!
Timepoint [8]
0
0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [9]
0
0
Progression Free Survival (PFS) for Brain Metastasis Based on mRECIST v1.1: SLI Phase and Phase 2
Query!
Assessment method [9]
0
0
PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression (PD) by Investigator assessment, or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase of at least 5 mm. If a participant did not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment.
Query!
Timepoint [9]
0
0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [10]
0
0
PFS for Global Tumor Assessment: SLI Phase and Phase 2
Query!
Assessment method [10]
0
0
PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression (PD) by Investigator assessment, or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of the diameters of target lesions, taking as a reference the smallest sum of diameters recorded since the treatment started (i.e., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of at least 5 mm. Global tumor assessment consists of brain metastasis and extracranial lesions. If a participant did not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment.
Query!
Timepoint [10]
0
0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [11]
0
0
BMRR Based on mRECIST v1.1: SLI Phase
Query!
Assessment method [11]
0
0
BMRR: percentage of participants who achieved a confirmed best overall response (BOR) of confirmed CR or PR in brain metastasis per mRECIST v1.1 from date of first dose until disease progression, death due to any cause, or start of subsequent anticancer therapy, whichever occurs first. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: Disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (e.g., percent change from baseline).
Query!
Timepoint [11]
0
0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months)
Query!
Secondary outcome [12]
0
0
Overall Survival: SLI Phase and Phase 2
Query!
Assessment method [12]
0
0
Overall survival (OS) was defined as the time from date of the first dose of study treatment to the date of death due to any cause. If a death was not observed by the date of the analysis cutoff, OS was censored at the date of last contact. OS (months) = (date of death or censoring - date of first dose +1)/30.4375
Query!
Timepoint [12]
0
0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Query!
Secondary outcome [13]
0
0
Number of Participants With Treatment Emergent AEs of Maximum Severity Grades Based on NCI CTCAE v4.03: Phase 2
Query!
Assessment method [13]
0
0
AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.TEAEs were events between 1st dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state or start of subsequent anticancer drug therapy minus 1 day, whichever occurs first.Severity was graded by NCI CTCAE v.4.03.Grade 1:asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2:moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3:severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL;Grade 4:life-threatening consequence, urgent intervention indicated; Grade 5:death related to AE. Only those categories in which at least 1 participant had data were reported.
Query!
Timepoint [13]
0
0
Day 1 of dosing up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [14]
0
0
Number of Participants With Hepatology Laboratory Test Abnormalities: Phase 2
Query!
Assessment method [14]
0
0
Hepatology laboratory abnormalities included following parameters: ALT, AST, ALT or AST >=3*ULN, >=5*ULN, >=10*ULN, >=20*ULN; TBILI: >=2*ULN; ALT >=3*ULN and TBILI >=2*ULN; AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP >2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP <=2*ULN or missing. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [14]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [15]
0
0
Number of Participants With Shift From Baseline for Hematology and Coagulation Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: Phase 2
Query!
Assessment method [15]
0
0
Hematology and coagulation laboratory test included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for hematology and coagulation laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [15]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [16]
0
0
Number of Participants With Shift From Baseline for Biochemistry Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: Phase 2
Query!
Assessment method [16]
0
0
Biochemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, CK increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, and serum amylase increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for biochemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Query!
Timepoint [16]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [17]
0
0
Number of Participants With Clinically Significant Change in Notable Abnormal Vital Signs: Phase 2
Query!
Assessment method [17]
0
0
In this outcome measure, number of participants with notable abnormal vital signs included: systolic and diastolic BP in mmHg based on following criteria: 1) High Systolic BP: >=160 mmHg and an increase >=20 mmHg from baseline; 2) High Diastolic BP: >=100 mmHg and an increase >=15 mmHg from baseline; 3) Low Systolic BP: <=90 mmHg with decrease from baseline of >=20 mmHg; 4) Low Diastolic BP: <=50 mmHg with decrease from baseline of >=15 mmHg; pulse rate in bpm based on following criteria: 1) High pulse rate >=120 bpm with increase from baseline of >=15 bpm; 2) Low pulse rate <=50 bpm with decrease from baseline of >=15 bpm; weight in kg based on following criteria: 1) Weight: Increase from baseline of >=10%, 2) Weight: >=20 % decrease from baseline; temperature in degree C based on following criteria: 1) High body temperature >=37.5 degree C, 2) Low body temperature <=36 degree C. Only those vital signs parameters in which at least 1 participant had data were reported.
Query!
Timepoint [17]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [18]
0
0
Number of Participants With Notable Abnormal Electrocardiogram (ECG) Values: Phase 2
Query!
Assessment method [18]
0
0
In this outcome measure, number of participants with notable abnormal ECG values included: QTcF values in msec based on following criteria: 1) increase from baseline >30 msec; 2) increase from baseline >60 msec; 3) new >450 msec; 4) new >480 msec; and 5) new >500 msec; heart rate values in bpm based on following criteria: 1) Increase from baseline >25% and to a value >100; 2) Decrease from baseline >25% and to a value <50. Only those vital ECG parameters in which at least 1 participant had data were reported.
Query!
Timepoint [18]
0
0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Query!
Secondary outcome [19]
0
0
Plasma Concentrations of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [19]
0
0
In this outcome measure, plasma concentrations (in nanogram per milliliter [ng/mL]) of encorafenib and its metabolite LHY746 at Cycle 1 Day 1 (C1D1), Cycle 1 Day 15 (C1D15), Cycle 2 Day 1 (C2D1), and Cycle 3 Day 1 (C3D1) at different time points were reported.
Query!
Timepoint [19]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [20]
0
0
Plasma Concentrations of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [20]
0
0
In this outcome measure, plasma concentrations of binimetinib and its metabolite AR00426032 at C1D1, C1D15, C2D1, and C3D1 at different time points were reported.
Query!
Timepoint [20]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [21]
0
0
Area Under the Plasma Concentration-Time Curve From Time Zero to 6 Hours (AUC 0-6) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [21]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to 6 hours (AUC 0-6) after administration of encorafenib and its metabolite LHY746 in nanogram*hour per milliliter (ng*hr/mL) at C1D1, and C1D15 were assessed.
Query!
Timepoint [21]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [22]
0
0
AUC0-6 of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [22]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to 6 hours (AUC 0-6) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [22]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [23]
0
0
Area Under the Plasma Concentration-time Curve From Time Zero to Last Time Point (AUClast) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [23]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to the last measurable time point (AUClast) after administration of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.
Query!
Timepoint [23]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [24]
0
0
AUClast of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [24]
0
0
In this outcome measure, area under the plasma concentration-time curve from zero to the last measurable time point (AUClast) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [24]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [25]
0
0
Area Under the Plasma Concentration-time Curve From Time Zero to Tau (AUCtau) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [25]
0
0
In this outcome measure, area under the plasma concentration-time curve from time zero to the last measurable time point Tau (AUCtau) of encorafenib and its metabolite LHY746 over a dosing interval (6 hours as appropriate) of C1D15 were assessed.
Query!
Timepoint [25]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [26]
0
0
AUCtau of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [26]
0
0
In this outcome measure, area under the plasma concentration-time curve from time zero to the last measurable time point Tau (AUCtau) of encorafenib and its metabolite LHY746 over a dosing interval (6 hours as appropriate) of C1D15 were assessed.
Query!
Timepoint [26]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [27]
0
0
Maximum Observed Plasma Concentration (Cmax) After Drug Administration of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [27]
0
0
In this outcome measure, maximum observed plasma concentration (Cmax) after administration of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.
Query!
Timepoint [27]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [28]
0
0
Cmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [28]
0
0
In this outcome measure, maximum observed plasma concentration (Cmax) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [28]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [29]
0
0
Minimum Observed Plasma Concentration (Cmin) at the End of a Dosing Interval at Steady State of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [29]
0
0
In this outcome measure, minimum observed plasma concentration (Cmin) after administration of encorafenib and its metabolite LHY746 at C1D15 were assessed.
Query!
Timepoint [29]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [30]
0
0
Cmin of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [30]
0
0
In this outcome measure, minimum observed plasma concentration (Cmin) after administration of binimetinib and its metabolite AR00426032 at C1D15 were assessed.
Query!
Timepoint [30]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [31]
0
0
Ctrough of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [31]
0
0
In this outcome measure, measured concentration at the end of a dosing interval (Ctrough) of encorafenib and its metabolite LHY746 at C1D15 were assessed.
Query!
Timepoint [31]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [32]
0
0
Ctrough of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [32]
0
0
In this outcome measure, measured concentration at the end of a dosing interval (Ctrough) of binimetinib and its metabolite AR00426032 at C1D15 were assessed.
Query!
Timepoint [32]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Query!
Secondary outcome [33]
0
0
Time to Reach Maximum Concentration (Tmax) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [33]
0
0
In this outcome measure, time to reach maximum concentration (Tmax) of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.
Query!
Timepoint [33]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [34]
0
0
Tmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [34]
0
0
In this outcome measure, time to reach maximum concentration (Tmax) of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.
Query!
Timepoint [34]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hrs (+/- 20 minutes [min]) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs (+/- 20 min) post-dose
Query!
Secondary outcome [35]
0
0
Time of Last PK Sample (Tlast) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [35]
0
0
In this outcome measure, time of last PK sample (Tlast) of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed. As outlined in the prespecified Statistical Analysis Plan for the study, since encorafenib was administered in continuous cycles, the pre-dose sample on Cycle 2 Day 1 was assumed to be at steady state and was interpolated as the concentration on 24 hours for encorafenib and LHY746 on Cycle 1 Day 15 during the analysis. In doing so, the reported Tlast values from the noncompartmental analysis (NCA) are 24 hours for encorafenib and LHY746.
Query!
Timepoint [35]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6, 24 hrs post-dose
Query!
Secondary outcome [36]
0
0
Tlast of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [36]
0
0
In this outcome measure, time of last PK sample (Tlast) of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed. As outlined in the prespecified Statistical Analysis Plan for the study, since binimetinib was administered in continuous cycles, the pre-dose sample on Cycle 2 Day 1 was assumed to be at steady state and was interpolated as the concentration for 12 hours for binimetinib and AR00426032 on Cycle 1 Day 15 for the noncompartmental analysis. In doing so, the reported Tlast values from the noncompartmental analysis (NCA) are 12 hours for binimetinib and AR00426032.
Query!
Timepoint [36]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6, 12 hrs post-dose
Query!
Secondary outcome [37]
0
0
Accumulation Ratio Between AUClast,ss and AUClast (RAUC) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [37]
0
0
In this outcome measure, accumulation ratio of encorafenib and its metabolite LHY746 calculated as: C1D15 AUC0-6 divided by C1D1 AUC0-6 was assessed.
Query!
Timepoint [37]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [38]
0
0
RAUC of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [38]
0
0
In this outcome measure, accumulation ratio of binimetinib and its metabolite AR00426032 calculated as: C1D15 AUC0-6 divided by C1D1 AUC0-6 was assessed.
Query!
Timepoint [38]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [39]
0
0
Accumulation Ratio Between Cmax,ss and Cmax (RCmax) of Encorafenib and Its Metabolite LHY746: SLI Phase
Query!
Assessment method [39]
0
0
In this outcome measure, accumulation ratio of encorafenib and its metabolite LHY746 calculated as: C1D15 Cmax divided by C1D1 Cmax was assessed.
Query!
Timepoint [39]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [40]
0
0
Rcmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Query!
Assessment method [40]
0
0
In this outcome measure, accumulation ratio of binimetinib and its metabolite AR00426032 calculated as: C1D15 Cmax divided by C1D1 Cmax was assessed.
Query!
Timepoint [40]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [41]
0
0
Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) of LHY746: SLI Phase
Query!
Assessment method [41]
0
0
In this outcome measure, ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, for LHY746/encorafenib at C1D1, and C1D15 was assessed.
Query!
Timepoint [41]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [42]
0
0
MRAUClast of AR00426032: SLI Phase
Query!
Assessment method [42]
0
0
In this outcome measure, ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, for AR00426032/binimetinib at C1D1, and C1D15 was assessed.
Query!
Timepoint [42]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [43]
0
0
Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) of LHY746: SLI Phase
Query!
Assessment method [43]
0
0
In this outcome measure, ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, for LHY746/encorafenib at C1D1, and C1D15 was assessed.
Query!
Timepoint [43]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Secondary outcome [44]
0
0
MRCmax of AR00426032: SLI Phase
Query!
Assessment method [44]
0
0
In this outcome measure, ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, for AR00426032/ binimetinib at C1D1, and C1D15 was assessed.
Query!
Timepoint [44]
0
0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Query!
Eligibility
Key inclusion criteria
Key
- Histologically confirmed diagnosis of cutaneous melanoma with metastases to the brain.
- Presence of B-RAF proto-oncogene, V600 mutant (BRAFV600) mutation in tumor tissue
previously determined by a local PCR or NGS-based assay at any time prior to Screening
or by a central laboratory during Screening.
- Must have at least 1 parenchymal brain lesion = 0.5 cm and = 4 cm, defined as a
magnetic resonance imaging (MRI) contrast-enhancing lesion that may be accurately
measured in at least 1 dimension. (Measurable intracranial lesions that have been
previously irradiated and have not been shown to be progressing following irradiation
should not be considered as target lesions).
- Patients may have received the following prior therapies:
1. Safety Lead-in, Phase 2 Randomized , Phase 2 Arm A Cohort 1: May have received
prior local therapy for brain metastases including but not restricted to brain
surgery, whole brain radiotherapy, stereotactic radiotherapy or stereotactic
radiosurgery. Multiple local (brain) therapies or combinations of local therapies
are allowed. For patients receiving local therapy to all brain lesions (including
WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in
longest diameter on baseline scan) or new measurable lesions are required. For
patients receiving local therapy for some but not all lesions, disease
progression based on RECIST 1.1 is not required as long as there are remaining
brain lesions that are measurable and not previously treated.
2. Phase 2 Arm A Cohort 2: Received no prior local therapy (e.g., brain surgery,
craniotomy, SRS or SRT) for brain metastases.
3. All patients (Safety Lead-In and Phase 2): May have received prior immunotherapy.
4. All patients (Safety Lead-In and Phase 2): If receiving concomitant
corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior
to first dose of study treatment (up to a total daily dose of 4mg of
dexamethasone or equivalent).
- An Eastern Cooperation Oncology Group Performance Status (ECOG PS) of 0 or 1 and
Karnofsky score = 80
- Adequate bone marrow, organ function and laboratory parameters
Key
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Patients with symptomatic brain metastasis.
- Uveal or mucosal melanoma.
- History of or current leptomeningeal metastases.
- Treatment with SRS or craniotomy within 14 days prior to start of study treatment, or
treatment with whole-brain radiation within 28 days prior to study treatment. Patients
who received local therapy should have complete recovery with no neurological
sequelae.
- Either of the following:
1. Radiation therapy to non-brain visceral metastasis within 2 weeks prior to start
of study treatment;
2. Continuous or intermittent small-molecule therapeutics or investigational agents
within 5 half-lives of the agent (or within 4 weeks prior to start of study
treatment, when half-life is unknown).
- Patients treated in the adjuvant setting with BRAF or MEK inhibitor(s) < 6 months
prior to enrollment. Patients who received BRAF or MEK inhibitors in the metastatic
setting are excluded.
- Patient has not recovered to = Grade 1 from toxic effects of prior therapy before
starting study treatment.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Other
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
30/04/2019
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
27/01/2022
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
13
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Crows Nest Eye Surgery - Crows Nest
Query!
Recruitment hospital [2]
0
0
Melanoma Institute Australia - North Sydney
Query!
Recruitment hospital [3]
0
0
Royal north shore center hospital dermatology clinics - st Leonards
Query!
Recruitment hospital [4]
0
0
Mater Imaging - Wollstonecraft
Query!
Recruitment postcode(s) [1]
0
0
2065 - Crows Nest
Query!
Recruitment postcode(s) [2]
0
0
2060 - North Sydney
Query!
Recruitment postcode(s) [3]
0
0
2065 - st Leonards
Query!
Recruitment postcode(s) [4]
0
0
2065 - Wollstonecraft
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Colorado
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Oregon
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Texas
Query!
Country [5]
0
0
Argentina
Query!
State/province [5]
0
0
Ciudad Autónoma DE Buenosaires
Query!
Country [6]
0
0
Argentina
Query!
State/province [6]
0
0
Santa FE
Query!
Country [7]
0
0
Argentina
Query!
State/province [7]
0
0
Caba
Query!
Country [8]
0
0
Belgium
Query!
State/province [8]
0
0
Antwerpen
Query!
Country [9]
0
0
Italy
Query!
State/province [9]
0
0
Naples
Query!
Country [10]
0
0
Italy
Query!
State/province [10]
0
0
Napoli
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Pfizer
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This is a multicenter, randomized open-label Phase 2 study to assess the safety, efficacy and
pharmacokinetic (PK) of 2 dosing regimens of encorafenib + binimetinib combination in
patients with BRAFV600-mutant melanoma with brain metastasis. Approximately 100 patients will
be enrolled, including 9 patients in a Safety Lead-in of the high-dose treatment arm. After a
Screening Period, treatment will be administered in 28-day cycles and will continue until
disease progression, unacceptable toxicity, withdrawal of consent, start of subsequent
anticancer therapy, death.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT03911869
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Pfizer CT.gov Call Center
Query!
Address
0
0
Pfizer
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03911869
Download to PDF