Status:

TERMINATED

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

Lead Sponsor:

Pfizer

Collaborating Sponsors:

Pierre Fabre Laboratories

Conditions:

Melanoma

Eligibility:

All Genders

12-17 years

Phase:

PHASE1

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 advanc...

Detailed Description

The study did not recruit the desired number of subjects and as a result does not have sufficient data for quantitative statistical analyses. Additionally, results data cannot be reported because doin...

Eligibility Criteria

Inclusion

  • 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 × 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

  • 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.

Key Trial Info

Start Date :

August 3 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

August 19 2022

Estimated Enrollment :

1 Patients enrolled

Trial Details

Trial ID

NCT03878719

Start Date

August 3 2020

End Date

August 19 2022

Last Update

April 3 2023

Active Locations (1)

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1

Fondazione IRCCS Istituto Nazionale Dei Tumori

Milan, Lombardy, Italy, 20133