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

NCT ID: NCT03878719

Last Updated: 2023-04-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-03
• Study Completion Date: 2022-08-19

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.

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 doing so would risk re-identification of the participant.

Conditions

Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

binimetinib

Intervention Type: DRUG

taken orally

encorafenib

Intervention Type: DRUG

taken orally

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.

Group Type: EXPERIMENTAL

binimetinib

Intervention Type: DRUG

taken orally

encorafenib

Intervention Type: DRUG

taken orally

Interventions

binimetinib

taken orally

Intervention Type: DRUG

encorafenib

taken orally

Intervention Type: DRUG

Eligibility Criteria

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

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pierre Fabre Laboratories

INDUSTRY

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Fondazione IRCCS Istituto Nazionale Dei Tumori

Milan, Lombardy, Italy

Countries

Italy

Related Links

https://pmiform.com/clinical-trial-info-request?StudyID=ARRAY-162-115

To obtain contact information for a study center near you, click here.

Other Identifiers

C4221011

Identifier Type: OTHER

Identifier Source: secondary_id

2018-001946-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ARRAY-162-115

Identifier Type: -

Identifier Source: org_study_id