Clinical Trials /

Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma

NCT03878719

Description:

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.

Related Conditions:
  • Melanoma of Unknown Primary
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: ARRAY-162-115
  • NCT ID: NCT03878719

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
binimetinibExpansion Phase
encorafenibExpansion Phase

Purpose

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 Arms

NameTypeDescriptionInterventions
Safety Run-in PhaseExperimentalbinimetinib 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.
  • binimetinib
  • encorafenib
Expansion PhaseExperimentalbinimetinib 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.
  • binimetinib
  • encorafenib

Eligibility Criteria

        Key Inclusion Criteria:

        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 × 10⁹/L;

               -  Hemoglobin ≥ 9 g/dL with or without transfusions;

               -  Platelets ≥ 75 × 10⁹/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 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 BRAFʷͭ or indeterminate melanoma in tumor tissue.
      
Maximum Eligible Age:17 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pharmacokinetic (PK) parameter (time to reach the maximum observed plasma concentration Cmax [Tmax]) for binimetinib
Time Frame:Day 1 and Day 15 of Cycle 1, 28 day cycles
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence and severity of adverse events (AEs)
Time Frame:From informed consent up to 30 days following last dose of study drug
Safety Issue:
Description:
Measure:Incidence of dose-limiting toxicities (DLTs)
Time Frame:Duration of treatment for safety run-in phase, approximately 6 months, 28 day cycles
Safety Issue:
Description:
Measure:Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for binimetinib
Time Frame:Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
Safety Issue:
Description:Five-point Hedonic scale from 1 to 5, 5=really good
Measure:Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for encorafenib
Time Frame:Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
Safety Issue:
Description:Five-point Hedonic scale from 1 to 5, 5=really good
Measure:Objective response rate (ORR) assessed by the investigator, based on Response Criteria Evaluation in Solid Tumors (RECIST) v1.1
Time Frame:Duration of treatment, approximately 6 months, 28 day cycles
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:Duration of treatment, approximately 6 months, 28 day cycles
Safety Issue:
Description:
Measure:Time to response
Time Frame:Duration of treatment, approximately 6 months, 28 day cycles
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Duration of treatment, approximately 6 months, 28 day cycles
Safety Issue:
Description:
Measure:One-year survival rate
Time Frame:From first dose up to 1 year after treatment initiation
Safety Issue:
Description:
Measure:Change from Baseline in bone densitometry based on dual energy X-ray absorptiometry (DEXA) scan.
Time Frame:Duration of treatment, approximately 6 months, 28 day cycles
Safety Issue:
Description:
Measure:Change from Baseline in calcium-phosphorus product (Ca × P)
Time Frame:Duration of treatment, approximately 6 months, 28 day cycles
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Array BioPharma

Trial Keywords

  • Adolescent
  • BRAF V600K
  • BRAF V600E

Last Updated

January 31, 2020