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Study of Efficacy and Safety of Dabrafenib and Trametinib Combination Therapy in Japanese Patients With BRAF V600E Stage IV NSCLC

Primary Purpose

Non-Small-Cell Lung Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Dabrafenib
Trametinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small-Cell Lung Cancer focused on measuring Non-Small-Cell Lung Cancer, NSCLC, dabrafenib, trametinib, Japanese patients, BRAF V600E mutation positive metastatic, stage IV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically- or cytologically-confirmed diagnosis of NSCLC stage IV (according to AJCC Staging 7th Edition)
  • Presence of a BRAF V600E mutation in lung cancer tissue. BRAF V600E mutation tested by local laboratory (e.g. study center laboratory, local laboratory company) with proper quality control and license to operation by local health authority is allowed.
  • Measurable disease according to RECIST v1.1.

Exclusion Criteria:

  • Previous treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, encorafenib, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, cobimetinib, binimetinib, AZD6244, and RDEA119) prior to start of study treatment

  • Patients with brain metastases are excluded if their brain metastases are:

    • Symptomatic OR
    • Treated (surgery, radiation therapy) but not clinically and radiographically stable 3 weeks after local therapy (as assessed by contrast enhanced magnetic resonance imaging [MRI] or computed tomography [CT]), OR
    • Asymptomatic and untreated but >1 cm in the longest dimension
  • History of malignancy with confirmed activating RAS mutation at any time.
  • History of interstitial lung disease or pneumonitis
  • A history or current evidence of retinal vein occlusion (RVO)
  • Current evidence of unstable aneurysm or one that needs treatment

Other protocol-defined inclusion/exclusion may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Dabrafenib +Trametinib

    Arm Description

    Oral Dabrafenib plus Oral Trametinib

    Outcomes

    Primary Outcome Measures

    Overall Response Rate (ORR) by investigator assessment
    ORR, defined as the percentage of patients with a confirmed CR or PR by investigator assessment as per RECIST v1.1 criteria

    Secondary Outcome Measures

    Duration of response (DOR)
    DOR, defined for the subset of patients with confirmed CR or PR, as the time from first documented evidence of CR or PR until time of first documented disease progression or death due to any cause.
    Disease control rate (DCR)
    DCR, defined as the proportion of patients with best overall response of CR, PR, or SD.
    Progression-free survival (PFS)
    PFS, defined as the interval between first dose and the earliest date of disease progression or death due to any cause.
    Overall survival (OS)
    OS, defined as the time from the date of first dose until death due to any cause.

    Full Information

    First Posted
    February 1, 2016
    Last Updated
    August 8, 2018
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02672358
    Brief Title
    Study of Efficacy and Safety of Dabrafenib and Trametinib Combination Therapy in Japanese Patients With BRAF V600E Stage IV NSCLC
    Official Title
    A Phase II, Multi-center, Single Arm, Open Label Study to Assess Efficacy and Safety of Dabrafenib and Trametinib Combination Therapy in Japanese Patients With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Company Decision
    Study Start Date
    September 3, 2018 (Anticipated)
    Primary Completion Date
    September 2, 2019 (Anticipated)
    Study Completion Date
    December 7, 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Novartis Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is an open-label, multicenter, non-randomized, single arm, phase II study to assess efficacy and safety of the dabrafenib and trametinib combination in Japanese patients with any line, stage IV NSCLC harboring a confirmed BRAF V600E mutation. Patients will receive oral dabrafenib twice daily and oral trametinib once daily combination therapy. Patients may continue study treatment until disease progression, unacceptable adverse events, start of a new anti-cancer therapy, consent withdrawal, death, or end of the study. Patients who have met the criteria for disease progression (PD) according to RECIST v1.1 may continue to receive study treatment if the investigator believes the patient is receiving clinical benefit and the patient is willing to continue on study treatment. After discontinuation of study treatment, all patients will be followed for survival until death, lost to follow-up, withdrawal of consent, or end of study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Non-Small-Cell Lung Cancer
    Keywords
    Non-Small-Cell Lung Cancer, NSCLC, dabrafenib, trametinib, Japanese patients, BRAF V600E mutation positive metastatic, stage IV

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Dabrafenib +Trametinib
    Arm Type
    Experimental
    Arm Description
    Oral Dabrafenib plus Oral Trametinib
    Intervention Type
    Drug
    Intervention Name(s)
    Dabrafenib
    Intervention Description
    Oral Dabrafenib 150 mg BID
    Intervention Type
    Drug
    Intervention Name(s)
    Trametinib
    Intervention Description
    Oral Trametinib 2 mg QD
    Primary Outcome Measure Information:
    Title
    Overall Response Rate (ORR) by investigator assessment
    Description
    ORR, defined as the percentage of patients with a confirmed CR or PR by investigator assessment as per RECIST v1.1 criteria
    Time Frame
    Approximately 2 years
    Secondary Outcome Measure Information:
    Title
    Duration of response (DOR)
    Description
    DOR, defined for the subset of patients with confirmed CR or PR, as the time from first documented evidence of CR or PR until time of first documented disease progression or death due to any cause.
    Time Frame
    Approximately 2 years
    Title
    Disease control rate (DCR)
    Description
    DCR, defined as the proportion of patients with best overall response of CR, PR, or SD.
    Time Frame
    Approximately 2 years
    Title
    Progression-free survival (PFS)
    Description
    PFS, defined as the interval between first dose and the earliest date of disease progression or death due to any cause.
    Time Frame
    Approximately 2 years
    Title
    Overall survival (OS)
    Description
    OS, defined as the time from the date of first dose until death due to any cause.
    Time Frame
    Approximately 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically- or cytologically-confirmed diagnosis of NSCLC stage IV (according to AJCC Staging 7th Edition) Presence of a BRAF V600E mutation in lung cancer tissue. BRAF V600E mutation tested by local laboratory (e.g. study center laboratory, local laboratory company) with proper quality control and license to operation by local health authority is allowed. Measurable disease according to RECIST v1.1. Exclusion Criteria: Previous treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, encorafenib, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, cobimetinib, binimetinib, AZD6244, and RDEA119) prior to start of study treatment Patients with brain metastases are excluded if their brain metastases are: Symptomatic OR Treated (surgery, radiation therapy) but not clinically and radiographically stable 3 weeks after local therapy (as assessed by contrast enhanced magnetic resonance imaging [MRI] or computed tomography [CT]), OR Asymptomatic and untreated but >1 cm in the longest dimension History of malignancy with confirmed activating RAS mutation at any time. History of interstitial lung disease or pneumonitis A history or current evidence of retinal vein occlusion (RVO) Current evidence of unstable aneurysm or one that needs treatment Other protocol-defined inclusion/exclusion may apply.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Novartis Pharmaceuticals
    Organizational Affiliation
    Novartis Pharmaceuticals
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    IPD Sharing Plan Description
    Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

    Learn more about this trial

    Study of Efficacy and Safety of Dabrafenib and Trametinib Combination Therapy in Japanese Patients With BRAF V600E Stage IV NSCLC

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