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Trial record 1 of 1 for:    NCT03911869
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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 : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE March 14, 2019
First Posted Date  ICMJE April 11, 2019
Last Update Posted Date September 21, 2020
Actual Study Start Date  ICMJE April 30, 2019
Estimated Primary Completion Date September 28, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2019)
  • Safety Lead-in: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
  • Safety Lead-in: Incidence and severity of adverse events (AEs) [ Time Frame: Up to 28 days ]
  • Safety Lead-in: Incidence of dose modifications due to AEs [ Time Frame: Up to 28 days ]
  • Safety Lead-in: Incidence of treatment discontinuations due to AEs [ Time Frame: Up to 28 days ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2020)
  • Extracranial response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Up to 24 months ]
  • 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.
  • Disease control rate (DCR) [ Time Frame: Up to 24 months ]
  • Duration of Response (DOR) [ Time Frame: Up to 24 months ]
  • Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
  • Brain metastasis response rate (BMRR) per mRECIST v1.1 for Safety Lead-in only [ Time Frame: Up to 24 months ]
  • Overall survival (OS) [ Time Frame: Up to 24 months ]
  • Incidence and severity of adverse events (AEs) [ Time Frame: Up to 24 months ]
  • Pharmacokinetics (PK) of binimetinib and its metabolite [ Time Frame: Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 2 and Cycle 3; 28 day cycles ]
    Plasma concentrations of binimetinib
  • Pharmacokinetics (PK) of encorafenib and its metabolite [ Time Frame: Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 2 and 3; 28 day cycles ]
    Plasma concentrations of encorafenib
Original Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2019)
  • Extracranial response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Up to 24 months ]
  • 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.
  • Disease control rate (DCR) [ Time Frame: Up to 24 months ]
  • Duration of Response (DOR) [ Time Frame: Up to 24 months ]
  • Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
  • Brain metastasis response rate (BMRR) per mRECIST v1.1 for Safety Lead-in only [ Time Frame: Up to 24 months ]
  • Overall survival (OS) [ Time Frame: Up to 24 months ]
  • Incidence and severity of adverse events (AEs) [ Time Frame: Up to 24 months ]
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
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 August 8, 2023
Estimated Primary Completion Date September 28, 2021   (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 Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
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/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date September 2020

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