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

Melanoma Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03878719
• Other study ID #: ARRAY-162-115
• Secondary ID: C42210112018-001
• Status: Terminated
• Phase: Phase 1
• Start date: August 3, 2020
• Est. completion date: August 19, 2022

Study information

• Verified date: March 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: August 19, 2022
• Est. primary completion date: August 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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 × 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 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.

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• binimetinib
taken orally
• encorafenib
taken orally

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale Dei Tumori	Milan	Lombardy

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Pierre Fabre Laboratories

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) parameter (time to reach the maximum observed plasma concentration Cmax [Tmax]) for binimetinib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Cmax) for binimetinib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (time of last PK sample [Tlast]) for binimetinib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (area under the plasma concentration-time curve from time zero to Tlast [AUClast]) for binimetinib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Tmax) for binimetinib's active metabolite (AR00426032)		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Cmax) for AR00426032		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Tlast) for AR00426032		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (AUClast) for AR00426032		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Tmax) for encorafenib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Cmax) for encorafenib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Tlast) for encorafenib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (AUClast) for encorafenib		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Tmax) for encorafenib's metabolite (LHY746)		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Cmax) for LHY746		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Tlast) for LHY746		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (AUClast) for LHY746		Day 1 and Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (trough concentration [Ctrough]) for binimetinib		at time zero Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (trough concentration [Ctrough]) for binimetinib		at time zero Day 1 of Cycle 2, 28 day cycles
Primary	PK parameter (trough concentration [Ctrough]) for binimetinib		at time zero Day 1 of Cycle 3, 28 day cycles
Primary	PK parameter (Ctrough) for AR00426032		at time zero Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Ctrough) for AR00426032		at time zero Day 1 of Cycle 2, 28 day cycles
Primary	PK parameter (Ctrough) for AR00426032		at time zero Day 1 of Cycle 3, 28 day cycles
Primary	PK parameter (Ctrough) for encorafenib		at time zero Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Ctrough) for encorafenib		at time zero Day 1 of Cycle 2, 28 day cycles
Primary	PK parameter (Ctrough) for encorafenib		at time zero Day 1 of Cycle 3, 28 day cycles
Primary	PK parameter (Ctrough) for LHY746		at time zero Day 15 of Cycle 1, 28 day cycles
Primary	PK parameter (Ctrough) for LHY746		at time zero Day 1 of Cycle 2, 28 day cycles
Primary	PK parameter (Ctrough) for LHY746		at time zero Day 1 of Cycle 3, 28 day cycles
Secondary	Incidence and severity of adverse events (AEs)		From informed consent up to 30 days following last dose of study drug
Secondary	Incidence of dose-limiting toxicities (DLTs)		Duration of treatment for safety run-in phase, approximately 6 months, 28 day cycles
Secondary	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	Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
Secondary	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	Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles
Secondary	Objective response rate (ORR) assessed by the investigator, based on Response Criteria Evaluation in Solid Tumors (RECIST) v1.1		Duration of treatment, approximately 6 months, 28 day cycles
Secondary	Duration of response (DOR)		Duration of treatment, approximately 6 months, 28 day cycles
Secondary	Time to response		Duration of treatment, approximately 6 months, 28 day cycles
Secondary	Progression-free survival (PFS)		Duration of treatment, approximately 6 months, 28 day cycles
Secondary	One-year survival rate		From first dose up to 1 year after treatment initiation
Secondary	Change from baseline bone age and the difference in bone age and chronological age		Duration of treatment, approximately 6 months, 28 day cycles
Secondary	Change from Baseline in bone densitometry based on dual energy X-ray absorptiometry (DEXA) scan.		Duration of treatment, approximately 6 months, 28 day cycles
Secondary	Change from Baseline in calcium-phosphorus product (Ca × P)		Duration of treatment, approximately 6 months, 28 day cycles

External Links

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