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An Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-mutant Melanoma Brain Metastasis

NCT03911869

Description:

This is a multicenter, randomized open-label Phase 2 study to assess the safety, efficacy and pharmacokinetic (PK) of 2 dosing regimens of encorafenib + binimetinib combination in patients with BRAFV600-mutant melanoma with brain metastasis. Approximately 100 patients will be enrolled, including 9 patients in a Safety Lead-in of the high-dose treatment arm. After a Screening Period, treatment will be administered in 28-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of subsequent anticancer therapy, death.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-mutant Melanoma Brain Metastasis
  • Official Title: A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-mutant Melanoma Brain Metastasis

Clinical Trial IDs

  • ORG STUDY ID: ARRAY-818-201
  • NCT ID: NCT03911869

Conditions

  • Brain Metastases

Interventions

DrugSynonymsArms
encorafenibStandard Dose Arm
binimetinibStandard Dose Arm

Purpose

This is a multicenter, randomized open-label Phase 2 study to assess the safety, efficacy and pharmacokinetic (PK) of 2 dosing regimens of encorafenib + binimetinib combination in patients with BRAFV600-mutant melanoma with brain metastasis. Approximately 100 patients will be enrolled, including 9 patients in a Safety Lead-in of the high-dose treatment arm. After a Screening Period, treatment will be administered in 28-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of subsequent anticancer therapy, death.

Trial Arms

NameTypeDescriptionInterventions
Standard Dose ArmExperimentalPatients in the standard-dose treatment arm will receive encorafenib and binimetinib in 28-day cycles. 450 mg encorafenib orally once a day (QD) 45 mg binimetinib orally twice a day (BID)
  • encorafenib
  • binimetinib
High Dose ArmExperimentalPatients in the high-dose treatment arm will receive encorafenib and binimetinib in 28-day cycles. 300 mg encorafenib orally twice a day (BID) 45 mg binimetinib orally twice a day (BID)
  • encorafenib
  • binimetinib

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically confirmed diagnosis of melanoma.

          -  Presence of B-RAF proto-oncogene, V600 mutant (BRAFV600) mutation in tumor tissue
             previously determined by a local assay at any time prior to Screening or by a central
             laboratory during Screening.

          -  Metastatic disease to the brain with at least 1 parenchymal brain lesion ≥ 0.5 cm and
             ≤ 4 cm, defined as a magnetic resonance imaging (MRI) contrast-enhancing lesion that
             may be accurately measured in at least 1 dimension.

          -  Patients may have received no more than 1 prior line of checkpoint inhibitor therapy.

          -  An Eastern Cooperation Oncology Group Performance Status (ECOG PS) of 0 or 1 and
             Karnofsky score ≥ 80

          -  Adequate bone marrow, organ function and laboratory parameters

        Key Exclusion Criteria:

          -  Patients with symptomatic brain metastasis.

          -  Patients requiring corticosteroids for brain metastasis.

          -  Uveal or mucosal melanoma.

          -  History of or current leptomeningeal metastases.

          -  Prior local treatment for brain metastasis, including whole brain radiation therapy,
             stereotactic radiosurgery or craniotomy.

          -  Either of the following:

               1. Radiation therapy to non-brain visceral metastasis within 2 weeks prior to start
                  of study treatment;

               2. Continuous or intermittent small-molecule therapeutics or investigational agents
                  within 5 half-lives of the agent (or within 4 weeks prior to start of study
                  treatment, when half-life is unknown).

          -  Patients treated in the adjuvant setting with BRAF or MEK inhibitor(s) < 12 months
             prior to enrollment. Patients treated in the adjuvant setting with B-RAF
             proto-oncogene, serine/threonine kinase (BRAF) or mitogen-activated protein kinase
             (MEK) inhibitors ≥ 12 months prior to enrollment are eligible. Patients who received
             BRAF or MEK inhibitors in the metastatic setting are excluded.

          -  Patient has not recovered to ≤ Grade 1 from toxic effects of prior therapy before
             starting study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety Lead-in: Incidence of dose-limiting toxicities (DLTs)
Time Frame:Up to 28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Extracranial response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Global response rate (brain metastasis response per mRECIST v1.1 and extracranial response per RECIST v1.1)
Time Frame:Up to 24 months
Safety Issue:
Description:Global response rate is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) per Investigator assessment for brain metastasis and extracranial lesions according to mRECIST v1.1 and RECIST v1.1, respectively.
Measure:Disease control rate (DCR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Brain metastasis response rate (BMRR) per mRECIST v1.1 for Safety Lead-in only
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence and severity of adverse events (AEs)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Pharmacokinetics (PK) of binimetinib and its metabolite
Time Frame:Day 1 and Day 15 of Cycle 1 and Day 1 of subsequent cycles; 28 day cycles
Safety Issue:
Description:Plasma concentrations of binimetinib
Measure:Pharmacokinetics (PK) of encorafenib and its metabolite
Time Frame:Day 1 and Day 15 of Cycle 1 and Day 1 of subsequent cycles; 28 day cycles
Safety Issue:
Description:Plasma concentrations of encorafenib

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Array BioPharma

Trial Keywords

  • BRAFV600-mutant
  • melanoma
  • brain metastasis

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