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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03878719
Registration number
NCT03878719
Ethics application status
Date submitted
20/02/2019
Date registered
18/03/2019
Date last updated
3/04/2023
Titles & IDs
Public title
Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma
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Scientific title
A Multicenter, Open-label Phase 1b Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma
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Secondary ID [1]
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C4221011
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Secondary ID [2]
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ARRAY-162-115
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - binimetinib
Treatment: Drugs - encorafenib
Experimental: Safety Run-in Phase - binimetinib taken twice daily (BID) and
encorafenib taken once daily (QD)
Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules are specified in the protocol.
Experimental: Expansion Phase - binimetinib taken twice daily (BID) and
encorafenib taken once daily (QD)
Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules and pediatric formulations are specified in the protocol.
Treatment: Drugs: binimetinib
taken orally
Treatment: Drugs: encorafenib
taken orally
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Pharmacokinetic (PK) parameter (time to reach the maximum observed plasma concentration Cmax [Tmax]) for binimetinib
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Assessment method [1]
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Timepoint [1]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [2]
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PK parameter (Cmax) for binimetinib
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Assessment method [2]
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Timepoint [2]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [3]
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PK parameter (time of last PK sample [Tlast]) for binimetinib
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Assessment method [3]
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Timepoint [3]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [4]
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PK parameter (area under the plasma concentration-time curve from time zero to Tlast [AUClast]) for binimetinib
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Assessment method [4]
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Timepoint [4]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [5]
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PK parameter (Tmax) for binimetinib's active metabolite (AR00426032)
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Assessment method [5]
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Timepoint [5]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [6]
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PK parameter (Cmax) for AR00426032
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Assessment method [6]
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Timepoint [6]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [7]
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PK parameter (Tlast) for AR00426032
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Assessment method [7]
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Timepoint [7]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [8]
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PK parameter (AUClast) for AR00426032
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Assessment method [8]
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Timepoint [8]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [9]
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PK parameter (Tmax) for encorafenib
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Assessment method [9]
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Timepoint [9]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [10]
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PK parameter (Cmax) for encorafenib
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Assessment method [10]
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Timepoint [10]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [11]
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PK parameter (Tlast) for encorafenib
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Assessment method [11]
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Timepoint [11]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [12]
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PK parameter (AUClast) for encorafenib
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Assessment method [12]
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Timepoint [12]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [13]
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PK parameter (Tmax) for encorafenib's metabolite (LHY746)
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Assessment method [13]
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Timepoint [13]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [14]
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PK parameter (Cmax) for LHY746
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Assessment method [14]
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Timepoint [14]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [15]
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PK parameter (Tlast) for LHY746
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Assessment method [15]
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Timepoint [15]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [16]
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PK parameter (AUClast) for LHY746
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Assessment method [16]
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Timepoint [16]
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Day 1 and Day 15 of Cycle 1, 28 day cycles
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Primary outcome [17]
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PK parameter (trough concentration [Ctrough]) for binimetinib
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Assessment method [17]
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Timepoint [17]
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at time zero Day 15 of Cycle 1, 28 day cycles
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Primary outcome [18]
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PK parameter (trough concentration [Ctrough]) for binimetinib
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Assessment method [18]
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Timepoint [18]
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at time zero Day 1 of Cycle 2, 28 day cycles
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Primary outcome [19]
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PK parameter (trough concentration [Ctrough]) for binimetinib
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Assessment method [19]
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Timepoint [19]
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at time zero Day 1 of Cycle 3, 28 day cycles
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Primary outcome [20]
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PK parameter (Ctrough) for AR00426032
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Assessment method [20]
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Timepoint [20]
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at time zero Day 15 of Cycle 1, 28 day cycles
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Primary outcome [21]
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PK parameter (Ctrough) for AR00426032
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Assessment method [21]
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Timepoint [21]
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at time zero Day 1 of Cycle 2, 28 day cycles
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Primary outcome [22]
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PK parameter (Ctrough) for AR00426032
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Assessment method [22]
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Timepoint [22]
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at time zero Day 1 of Cycle 3, 28 day cycles
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Primary outcome [23]
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PK parameter (Ctrough) for encorafenib
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Assessment method [23]
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Timepoint [23]
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at time zero Day 15 of Cycle 1, 28 day cycles
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Primary outcome [24]
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PK parameter (Ctrough) for encorafenib
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Assessment method [24]
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Timepoint [24]
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at time zero Day 1 of Cycle 2, 28 day cycles
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Primary outcome [25]
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PK parameter (Ctrough) for encorafenib
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Assessment method [25]
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Timepoint [25]
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at time zero Day 1 of Cycle 3, 28 day cycles
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Primary outcome [26]
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PK parameter (Ctrough) for LHY746
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Assessment method [26]
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Timepoint [26]
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at time zero Day 15 of Cycle 1, 28 day cycles
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Primary outcome [27]
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PK parameter (Ctrough) for LHY746
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Assessment method [27]
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Timepoint [27]
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at time zero Day 1 of Cycle 2, 28 day cycles
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Primary outcome [28]
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PK parameter (Ctrough) for LHY746
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Assessment method [28]
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Timepoint [28]
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at time zero Day 1 of Cycle 3, 28 day cycles
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Secondary outcome [1]
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Incidence and severity of adverse events (AEs)
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Assessment method [1]
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Timepoint [1]
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From informed consent up to 30 days following last dose of study drug
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Secondary outcome [2]
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Incidence of dose-limiting toxicities (DLTs)
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Assessment method [2]
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Timepoint [2]
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Duration of treatment for safety run-in phase, approximately 6 months, 28 day cycles
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Secondary outcome [3]
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Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for binimetinib
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Assessment method [3]
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Five-point Hedonic scale from 1 to 5, 5=really good
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Timepoint [3]
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Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
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Secondary outcome [4]
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Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for encorafenib
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Assessment method [4]
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Five-point Hedonic scale from 1 to 5, 5=really good
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Timepoint [4]
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Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
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Secondary outcome [5]
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Objective response rate (ORR) assessed by the investigator, based on Response Criteria Evaluation in Solid Tumors (RECIST) v1.1
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Assessment method [5]
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Timepoint [5]
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Duration of treatment, approximately 6 months, 28 day cycles
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Secondary outcome [6]
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Duration of response (DOR)
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Assessment method [6]
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Timepoint [6]
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Duration of treatment, approximately 6 months, 28 day cycles
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Secondary outcome [7]
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Time to response
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Assessment method [7]
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Timepoint [7]
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Duration of treatment, approximately 6 months, 28 day cycles
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Secondary outcome [8]
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Progression-free survival (PFS)
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Assessment method [8]
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Timepoint [8]
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Duration of treatment, approximately 6 months, 28 day cycles
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Secondary outcome [9]
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One-year survival rate
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Assessment method [9]
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Timepoint [9]
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From first dose up to 1 year after treatment initiation
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Secondary outcome [10]
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Change from baseline bone age and the difference in bone age and chronological age
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Assessment method [10]
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Timepoint [10]
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Duration of treatment, approximately 6 months, 28 day cycles
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Secondary outcome [11]
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Change from Baseline in bone densitometry based on dual energy X-ray absorptiometry (DEXA) scan.
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Assessment method [11]
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Timepoint [11]
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Duration of treatment, approximately 6 months, 28 day cycles
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Secondary outcome [12]
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Change from Baseline in calcium-phosphorus product (Ca × P)
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Assessment method [12]
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Timepoint [12]
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Duration of treatment, approximately 6 months, 28 day cycles
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Eligibility
Key inclusion criteria
Key
Patients must meet all of the following criteria to be eligible for enrollment in the
study.
- Histologically confirmed diagnosis of locally advanced, unresectable or metastatic
cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer
Stage IIIB, IIIC, or IV.
- Presence of BRAF V600E or V600K mutation in tumor tissue as determined by a local or
central laboratory
- Adequate cardiac function:
- Left ventricular ejection fraction (LVEF) = 50% as determined by ECHO or
multi-gated acquisition (MUGA) scan and above the institutional lower limit of
normal (LLN);
- Triplicate average baseline QTcF value = 450 ms.
- Adequate bone marrow, organ function, and laboratory parameters:
- Absolute neutrophil count (ANC) = 1.5 × 10?/L;
- Hemoglobin = 9 g/dL with or without transfusions;
- Platelets = 75 × 10?/L without transfusions;
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 2.5 ×
upper limit of normal (ULN); in patients with liver metastases = 5 × ULN;
- Total bilirubin = 1.5 × ULN;
- Creatinine = 1.5 × institutional ULN for age, or calculated creatinine clearance
= 70 mL/min/1.73 m² (following Schwartz formula).
- Adequate performance status at Screening:
- Patients < 16 years old: Lansky Performance Scale score = 80
- Patients 16 to 17 years old: Karnofsky Performance Scale score = 80
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Minimum age
12
Years
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Maximum age
17
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Patients meeting any of the following criteria are not eligible for enrollment in the
study.
- Uveal or mucosal melanoma.
- Brain metastases that are uncontrolled or symptomatic, require steroids, are
potentially life-threatening or have required radiation within 28 days prior to
starting study drug.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors
for RVO
- Prior therapy with a BRAF inhibitor (e.g., dabrafenib, vemurafenib) and/or a MEK
inhibitor (e.g., trametinib, cobimetinib).
- Impaired cardiovascular function or clinically significant cardiovascular disease,
including any of the following:
- History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6
months prior to screening,
- Symptomatic chronic heart failure, history or current evidence of clinically
significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to
screening except atrial fibrillation and paroxysmal supraventricular tachycardia.
- Concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
- Uncontrolled arterial hypertension despite medical treatment
- Presence of BRAF?? or indeterminate melanoma in tumor tissue.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
3/08/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
19/08/2022
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Sample size
Target
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Accrual to date
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Final
1
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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Italy
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State/province [1]
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Lombardy
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Pfizer
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Pierre Fabre Laboratories
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a multicenter Phase 1b, open-label study to evaluate the pharmacokinetic, safety and
efficacy of binimetinib and encorafenib co-administered to adolescent patients with BRAF
V600-mutant advanced/metastatic melanoma. The study consists of a Safety Run-in Phase to
determine the RDE (recommended dose in expansion), followed by an Expansion Phase.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03878719
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Trial related presentations / publications
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Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed
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Contacts
Principal investigator
Name
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Pfizer Pfizer CT.gov Call Center
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Address
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Pfizer
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03878719
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