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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 (POLARIS)

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ClinicalTrials.gov Identifier: NCT03911869
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Brain Metastases Drug: encorafenib Drug: binimetinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Standard Dose Arm

Patients 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)
Drug: encorafenib
taken orally

Drug: binimetinib
taken orally

Experimental: High Dose Arm

Patients 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)
Drug: encorafenib
taken orally

Drug: binimetinib
taken orally




Primary Outcome Measures :
  1. Safety Lead-in: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
  2. Safety Lead-in: Incidence and severity of adverse events (AEs) [ Time Frame: Up to 28 days ]
  3. Safety Lead-in: Incidence of dose modifications due to AEs [ Time Frame: Up to 28 days ]
  4. Safety Lead-in: Incidence of treatment discontinuations due to AEs [ Time Frame: Up to 28 days ]
  5. Phase 2: Brain metastasis response rate (BMRR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v1.1) [ Time Frame: Up to 24 months ]

Secondary Outcome Measures :
  1. Extracranial response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Up to 24 months ]
  2. Global response rate (brain metastasis response per mRECIST v1.1 and extracranial response per RECIST v1.1) [ Time Frame: Up to 24 months ]
    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.

  3. Disease control rate (DCR) [ Time Frame: Up to 24 months ]
  4. Duration of Response (DOR) [ Time Frame: Up to 24 months ]
  5. Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
  6. Brain metastasis response rate (BMRR) per mRECIST v1.1 for Safety Lead-in only [ Time Frame: Up to 24 months ]
  7. Overall survival (OS) [ Time Frame: Up to 24 months ]
  8. Incidence and severity of adverse events (AEs) [ Time Frame: Up to 24 months ]
  9. 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 ]
    Plasma concentrations of binimetinib

  10. 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 ]
    Plasma concentrations of encorafenib



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03911869


Contacts
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Contact: Array BioPharma, Inc 303-381-6604 clinicaltrials@arraybiopharma.com

Locations
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United States, California
Array BioPharma Investigative Site Recruiting
Los Angeles, California, United States, 90025
United States, Texas
Array BioPharma Investigative Site Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Array BioPharma
Investigators
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Study Director: Study Director Array BioPharma, Inc

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Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT03911869     History of Changes
Other Study ID Numbers: ARRAY-818-201
First Posted: April 11, 2019    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Array BioPharma:
BRAFV600-mutant
melanoma
brain metastasis

Additional relevant MeSH terms:
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Melanoma
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases