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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03878719




Registration number
NCT03878719
Ethics application status
Date submitted
20/02/2019
Date registered
18/03/2019
Date last updated
5/02/2020

Titles & IDs
Public title
Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma
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
Secondary ID [1] 0 0
ARRAY-162-115
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetic (PK) parameter (time to reach the maximum observed plasma concentration Cmax [Tmax]) for binimetinib
Timepoint [1] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [2] 0 0
PK parameter (Cmax) for binimetinib
Timepoint [2] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [3] 0 0
PK parameter (time of last PK sample [Tlast]) for binimetinib
Timepoint [3] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [4] 0 0
PK parameter (area under the plasma concentration-time curve from time zero to Tlast [AUClast]) for binimetinib
Timepoint [4] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [5] 0 0
PK parameter (Tmax) for binimetinib's active metabolite (AR00426032)
Timepoint [5] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [6] 0 0
PK parameter (Cmax) for AR00426032
Timepoint [6] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [7] 0 0
PK parameter (Tlast) for AR00426032
Timepoint [7] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [8] 0 0
PK parameter (AUClast) for AR00426032
Timepoint [8] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [9] 0 0
PK parameter (Tmax) for encorafenib
Timepoint [9] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [10] 0 0
PK parameter (Cmax) for encorafenib
Timepoint [10] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [11] 0 0
PK parameter (Tlast) for encorafenib
Timepoint [11] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [12] 0 0
PK parameter (AUClast) for encorafenib
Timepoint [12] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [13] 0 0
PK parameter (Tmax) for encorafenib's metabolite (LHY746)
Timepoint [13] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [14] 0 0
PK parameter (Cmax) for LHY746
Timepoint [14] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [15] 0 0
PK parameter (Tlast) for LHY746
Timepoint [15] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [16] 0 0
PK parameter (AUClast) for LHY746
Timepoint [16] 0 0
Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary outcome [17] 0 0
PK parameter (trough concentration [Ctrough]) for binimetinib
Timepoint [17] 0 0
at time zero Day 15 of Cycle 1, 28 day cycles
Primary outcome [18] 0 0
PK parameter (trough concentration [Ctrough]) for binimetinib
Timepoint [18] 0 0
at time zero Day 1 of Cycle 2, 28 day cycles
Primary outcome [19] 0 0
PK parameter (trough concentration [Ctrough]) for binimetinib
Timepoint [19] 0 0
at time zero Day 1 of Cycle 3, 28 day cycles
Primary outcome [20] 0 0
PK parameter (Ctrough) for AR00426032
Timepoint [20] 0 0
at time zero Day 15 of Cycle 1, 28 day cycles
Primary outcome [21] 0 0
PK parameter (Ctrough) for AR00426032
Timepoint [21] 0 0
at time zero Day 1 of Cycle 2, 28 day cycles
Primary outcome [22] 0 0
PK parameter (Ctrough) for AR00426032
Timepoint [22] 0 0
at time zero Day 1 of Cycle 3, 28 day cycles
Primary outcome [23] 0 0
PK parameter (Ctrough) for encorafenib
Timepoint [23] 0 0
at time zero Day 15 of Cycle 1, 28 day cycles
Primary outcome [24] 0 0
PK parameter (Ctrough) for encorafenib
Timepoint [24] 0 0
at time zero Day 1 of Cycle 2, 28 day cycles
Primary outcome [25] 0 0
PK parameter (Ctrough) for encorafenib
Timepoint [25] 0 0
at time zero Day 1 of Cycle 3, 28 day cycles
Primary outcome [26] 0 0
PK parameter (Ctrough) for LHY746
Timepoint [26] 0 0
at time zero Day 15 of Cycle 1, 28 day cycles
Primary outcome [27] 0 0
PK parameter (Ctrough) for LHY746
Timepoint [27] 0 0
at time zero Day 1 of Cycle 2, 28 day cycles
Primary outcome [28] 0 0
PK parameter (Ctrough) for LHY746
Timepoint [28] 0 0
at time zero Day 1 of Cycle 3, 28 day cycles
Secondary outcome [1] 0 0
Incidence and severity of adverse events (AEs)
Timepoint [1] 0 0
From informed consent up to 30 days following last dose of study drug
Secondary outcome [2] 0 0
Incidence of dose-limiting toxicities (DLTs)
Timepoint [2] 0 0
Duration of treatment for safety run-in phase, approximately 6 months, 28 day cycles
Secondary outcome [3] 0 0
Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for binimetinib - Five-point Hedonic scale from 1 to 5, 5=really good
Timepoint [3] 0 0
Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
Secondary outcome [4] 0 0
Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for encorafenib - Five-point Hedonic scale from 1 to 5, 5=really good
Timepoint [4] 0 0
Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
Secondary outcome [5] 0 0
Objective response rate (ORR) assessed by the investigator, based on Response Criteria Evaluation in Solid Tumors (RECIST) v1.1
Timepoint [5] 0 0
Duration of treatment, approximately 6 months, 28 day cycles
Secondary outcome [6] 0 0
Duration of response (DOR)
Timepoint [6] 0 0
Duration of treatment, approximately 6 months, 28 day cycles
Secondary outcome [7] 0 0
Time to response
Timepoint [7] 0 0
Duration of treatment, approximately 6 months, 28 day cycles
Secondary outcome [8] 0 0
Progression-free survival (PFS)
Timepoint [8] 0 0
Duration of treatment, approximately 6 months, 28 day cycles
Secondary outcome [9] 0 0
One-year survival rate
Timepoint [9] 0 0
From first dose up to 1 year after treatment initiation
Secondary outcome [10] 0 0
Change from Baseline in bone densitometry based on dual energy X-ray absorptiometry (DEXA) scan.
Timepoint [10] 0 0
Duration of treatment, approximately 6 months, 28 day cycles
Secondary outcome [11] 0 0
Change from Baseline in calcium-phosphorus product (Ca × P)
Timepoint [11] 0 0
Duration of treatment, approximately 6 months, 28 day cycles

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

Key
Minimum age
12 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Pennsylvania
Country [2] 0 0
Czechia
State/province [2] 0 0
Praha
Country [3] 0 0
Italy
State/province [3] 0 0
Lombardy
Country [4] 0 0
Italy
State/province [4] 0 0
Tuscany
Country [5] 0 0
Italy
State/province [5] 0 0
Napoli
Country [6] 0 0
Italy
State/province [6] 0 0
Turin
Country [7] 0 0
New Zealand
State/province [7] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Array BioPharma
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Pierre Fabre Laboratories
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT03878719
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Array BioPharma, Inc
Address 0 0
Country 0 0
Phone 0 0
303-381-6604
Fax 0 0
Email 0 0
clinicaltrials@arraybiopharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03878719