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

NCT02672358

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CDRB436E1201
  • NCT ID: NCT02672358

Conditions

  • Non-Small-Cell Lung Cancer

Interventions

DrugSynonymsArms
DabrafenibDabrafenib +Trametinib
TrametinibDabrafenib +Trametinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dabrafenib +TrametinibExperimentalOral Dabrafenib plus Oral Trametinib
  • Dabrafenib
  • Trametinib

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) by investigator assessment
Time Frame:Approximately 2 years
Safety Issue:
Description: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

Measure:Duration of response (DOR)
Time Frame:Approximately 2 years
Safety Issue:
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.
Measure:Disease control rate (DCR)
Time Frame:Approximately 2 years
Safety Issue:
Description:DCR, defined as the proportion of patients with best overall response of CR, PR, or SD.
Measure:Progression-free survival (PFS)
Time Frame:Approximately 2 years
Safety Issue:
Description:PFS, defined as the interval between first dose and the earliest date of disease progression or death due to any cause.
Measure:Overall survival (OS)
Time Frame:Approximately 2 years
Safety Issue:
Description:OS, defined as the time from the date of first dose until death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Non-Small-Cell Lung Cancer
  • NSCLC
  • dabrafenib
  • trametinib
  • Japanese patients
  • BRAF V600E mutation positive metastatic
  • stage IV

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