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

Last updated date
Study Location
UZ Antwerpen Pharmacy
Edegem, Antwerpen, 02650, Belgium
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Brain Metastases
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Histologically confirmed diagnosis of cutaneous melanoma with metastases to the brain.

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

- Must have 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. (Measurable intracranial lesions that have been previously irradiated and have not been shown to be progressing following irradiation should not be considered as target lesions).

- Patients may have received the following prior therapies:

1. Safety Lead-in, Phase 2 Randomized , Phase 2 Arm A Cohort 1: May have received prior local therapy for brain metastases including but not restricted to brain surgery, whole brain radiotherapy, stereotactic radiotherapy or stereotactic radiosurgery. Multiple local (brain) therapies or combinations of local therapies are allowed. For patients receiving local therapy to all brain lesions (including WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in longest diameter on baseline scan) or new measurable lesions are required. For patients receiving local therapy for some but not all lesions, disease progression based on RECIST 1.1 is not required as long as there are remaining brain lesions that are measurable and not previously treated.

2. Phase 2 Arm A Cohort 2: Received no prior local therapy (e.g., brain surgery, craniotomy, SRS or SRT) for brain metastases.

3. All patients (Safety Lead-In and Phase 2): May have received prior immunotherapy.

4. All patients (Safety Lead-In and Phase 2): If receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to first dose of study treatment (up to a total daily dose of 4mg of dexamethasone or equivalent).

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Patients with symptomatic brain metastasis.


- Uveal or mucosal melanoma.


- History of or current leptomeningeal metastases.


- Treatment with SRS or craniotomy within 14 days prior to start of study treatment, or
treatment with whole-brain radiation within 28 days prior to study treatment. Patients
who received local therapy should have complete recovery with no neurological
sequelae.


- 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) < 6 months
prior to enrollment. 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.

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Brain MetastasesAn 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
  1. Edegem, Antwerpen
  2. Napoli, Naples
  3. Encinitas, California
  4. Los Angeles, California
  5. Orange, California
  6. San Francisco, California
  7. San Francisco, California
  8. San Francisco, California
  9. San Francisco, California
  10. San Francisco, California
  11. San Marcos, California
  12. Aurora, Colorado
  13. Aurora, Colorado
  14. Aurora, Colorado
  15. Aurora, Colorado
  16. Aurora, Colorado
  17. Boston, Massachusetts
  18. Boston, Massachusetts
  19. Boston, Massachusetts
  20. Ann Arbor, Michigan
  21. Ann Arbor, Michigan
  22. Ann Arbor, Michigan
  23. Grand Haven, Michigan
  24. Grand Haven, Michigan
  25. Grand Rapids, Michigan
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  27. Grand Rapids, Michigan
  28. Holland, Michigan
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  30. Muskegon, Michigan
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  32. Norton Shores, Michigan
  33. Zeeland, Michigan
  34. Creve Coeur, Missouri
  35. Kansas City, Missouri
  36. Saint Louis, Missouri
  37. Saint Louis, Missouri
  38. Saint Louis, Missouri
  39. Saint Louis, Missouri
  40. Elmwood Park, New Jersey
  41. Hackensack, New Jersey
  42. Morristown, New Jersey
  43. Paramus, New Jersey
  44. Phillipsburg, New Jersey
  45. Phillipsburg, New Jersey
  46. Summit, New Jersey
  47. West Orange, New Jersey
  48. New York, New York
  49. New York, New York
  50. New York, New York
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  53. Durham, North Carolina
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  56. Columbus, Ohio
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  62. Gresham, Oregon
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  65. Portland, Oregon
  66. Portland, Oregon
  67. Portland, Oregon
  68. Portland, Oregon
  69. Portland, Oregon
  70. Tualatin, Oregon
  71. Allentown, Pennsylvania
  72. Bethlehem, Pennsylvania
  73. Bethlehem, Pennsylvania
  74. Bethlehem, Pennsylvania
  75. Coaldale, Pennsylvania
  76. Easton, Pennsylvania
  77. Easton, Pennsylvania
  78. Pittsburgh, Pennsylvania
  79. Pittsburgh, Pennsylvania
  80. Pittsburgh, Pennsylvania
  81. Pittsburgh, Pennsylvania
  82. Quakertown, Pennsylvania
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  84. Nashville, Tennessee
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  90. Salt Lake City, Utah
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  93. Madison, Wisconsin
  94. Buenos Aires, Ciudad Autónoma DE Buenosaires
  95. Rosario, Santa FE
  96. Rosario, Santa FE
  97. Rosario, Santa FE
  98. Rosario, Santa FE
  99. Caba,
  100. Rosario,
  101. Coffs Harbour, New South Wales
  102. Crows Nest, New South Wales
  103. st Leonards, New South Wales
  104. Wollstonecraft, New South Wales
  105. Wollstonecraft, New South Wales
  106. Adelaide, South Australia
  107. Adelaide, South Australia
  108. Bedford park, South Australia
  109. Seacombe Gardens, South Australia
  110. Melbourne, Victoria
  111. Melbourne, Victoria
  112. Nedlands, Western Australia
  113. Nedlands,
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  115. Wilrijk, Antwerpen
  116. Kortrijk,
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  118. Milano, Milan
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  120. Napoli, Naples
  121. Padova, Padua
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  123. Padova, Veneto
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ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Metastases
Intervention  ICMJE
  • Drug: encorafenib
    taken orally
  • Drug: binimetinib
    taken orally
Study Arms  ICMJE
  • 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)

    Patients who are able to tolerate the standard dose during the first 4 weeks of treatment (Cycle 1) should be dose-escalated to 600 mg encorafenib QD plus 45 mg binimetinib BID provided they meet protocol-defined criteria.

    Interventions:
    • Drug: encorafenib
    • Drug: binimetinib
  • 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)
    Interventions:
    • Drug: encorafenib
    • Drug: binimetinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2020)
110
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2019)
100
Estimated Study Completion Date  ICMJE September 29, 2023
Estimated Primary Completion Date May 26, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Histologically confirmed diagnosis of cutaneous melanoma with metastases to the brain.
  • Presence of B-RAF proto-oncogene, V600 mutant (BRAFV600) mutation in tumor tissue previously determined by a local PCR or NGS-based assay at any time prior to Screening or by a central laboratory during Screening.
  • Must have 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. (Measurable intracranial lesions that have been previously irradiated and have not been shown to be progressing following irradiation should not be considered as target lesions).
  • Patients may have received the following prior therapies:

    1. Safety Lead-in, Phase 2 Randomized , Phase 2 Arm A Cohort 1: May have received prior local therapy for brain metastases including but not restricted to brain surgery, whole brain radiotherapy, stereotactic radiotherapy or stereotactic radiosurgery. Multiple local (brain) therapies or combinations of local therapies are allowed. For patients receiving local therapy to all brain lesions (including WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in longest diameter on baseline scan) or new measurable lesions are required. For patients receiving local therapy for some but not all lesions, disease progression based on RECIST 1.1 is not required as long as there are remaining brain lesions that are measurable and not previously treated.
    2. Phase 2 Arm A Cohort 2: Received no prior local therapy (e.g., brain surgery, craniotomy, SRS or SRT) for brain metastases.
    3. All patients (Safety Lead-In and Phase 2): May have received prior immunotherapy.
    4. All patients (Safety Lead-In and Phase 2): If receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to first dose of study treatment (up to a total daily dose of 4mg of dexamethasone or equivalent).
  • 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.
  • Uveal or mucosal melanoma.
  • History of or current leptomeningeal metastases.
  • Treatment with SRS or craniotomy within 14 days prior to start of study treatment, or treatment with whole-brain radiation within 28 days prior to study treatment. Patients who received local therapy should have complete recovery with no neurological sequelae.
  • 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) < 6 months prior to enrollment. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Canada,   Italy,   New Zealand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03911869
Other Study ID Numbers  ICMJE ARRAY-818-201
C4221006 ( Other Identifier: Alias Study Number )
2018-004555-21 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP