Clinical Trials /

Dabrafenib and Trametinib in Patients With Non-small Cell Lung Cancer Harboring V600E BRAF Mutation

NCT03543306

Description:

This is a Phase II, non-randomized, open-label study to assess the efficacy, safety, and tolerability of dabrafenib and trametinib in stage IV disease to subjects with BRAF V600E mutant advanced non-small cell lung cancer. Subjects will receive dabrafenib 150 mg bid and trametinib 2 mg once daily in combination therapy and continue on treatment until disease progression, death, or unacceptable adverse event.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dabrafenib and Trametinib in Patients With Non-small Cell Lung Cancer Harboring V600E BRAF Mutation
  • Official Title: An Open-label, Multicenter, Phase II Study of Dabrafenib and Trametinib in Patients With Non-small Cell Lung Cancer Harboring V600E BRAF Mutation

Clinical Trial IDs

  • ORG STUDY ID: STARTER_BRAF
  • NCT ID: NCT03543306

Conditions

  • Cancer
  • Lung Cancer Metastatic
  • BRAF V600E

Interventions

DrugSynonymsArms
daborafenib plus trametinib

Purpose

This is a Phase II, non-randomized, open-label study to assess the efficacy, safety, and tolerability of dabrafenib and trametinib in stage IV disease to subjects with BRAF V600E mutant advanced non-small cell lung cancer. Subjects will receive dabrafenib 150 mg bid and trametinib 2 mg once daily in combination therapy and continue on treatment until disease progression, death, or unacceptable adverse event.

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

        Subjects with histologically or cytologically confirmed, unresectable stage IIIB/IV NSCLC
        that carries a V600 BRAF mutation, as per NGS ECOG performance status of 0 to 2 Male or
        female; ≥ 18 Subjects with measurable lesion (using RECIST 1.1 criteria) Subjects must have
        archival tissue sample available, collected either at the time of diagnosis of NSCLC or any
        time since Patients who have progressed during or after 1st line or 2nd line therapy prior
        to the first dose of dabrafenib/trametinib. For patient who have received prior platinum
        containing adjuvant, neoadjuvant, or definitive chemoradiation for locally advanced
        disease, those treatments are regarded as 1st line if the progression has occurred < 12
        months from last therapy.

        Subjects who meet the following criteria:

        Absolute neutrophil count (ANC) >1.5 x 109/L Platelet count >100 x 109/L Serum creatinine
        >1.5 x upper limit of normal (ULN) AST (SGOT) and ALT (SGPT) > 3 x upper limit of normal
        (ULN) (If there is Liver Metastasis > 5 x upper limit of normal (ULN)) Total bilirubin>1.5
        x upper limit of normal (ULN) the progression has occurred < 12 months from last therapy.
        Patients with asymptomatic brain metastasis could be eligible. Provision of written
        informed consent prior to any study specific procedures

        Exclusion Criteria:

        Any major operation or irradiation within 4 weeks of baseline disease assessment Any
        clinically significant gastrointestinal abnormalities which may impair intake or absorption
        of the study drug Subjects with symptomatic central nervous system (CNS) metastases who are
        neurologically unstable or have required increasing doses of steroids within the 2 weeks
        prior to study entry to manage CNS symptoms Subjects with chemotherapy naïve or those who
        already had received two lines of chemotherapy including immunotherapy or targeted therapy.

        Other co-existing malignancies or malignancies diagnosed within the last 3 years with the
        exception of basal cell carcinoma or cervical cancer in situ.

        Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months,
        unstable angina within 6 months, over NYHA class III congestive heart failure, congenital
        long QT syndrome, 2° or more AV Block and uncontrolled hypertension) Patients with known
        history of extensive disseminated bilateral interstitial fibrosis or interstitial lung
        disease, including a history of drug pneumonitis, hypersensitivity pneumonitis,
        obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e.
        affecting activities of daily living or requiring therapeutic intervention).

        Pregnant or lactating female Evidence of any other significant clinical disorder or
        laboratory finding that makes it undesirable for the patient to participate in the study

        Receiving medications that meet one of the following criteria and that cannot be
        discontinued at least 1 week prior to the start of treatment with IPs for the duration of
        participation:

        Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes
        (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm) Strong
        inhibitors or strong inducers of CYP2C8 and CYP3A4 Unstable or increasing doses of
        corticosteroids enzyme-inducing anticonvulsive agents herbal supplements Patients who have
        received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study
        treatment or patients who have not recovered from radiotherapy-related toxicities. For all
        other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy
        ≤ 2 weeks prior to starting the study treatment or patients who have not recovered from
        radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior
        to starting study treatment is allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months
Safety Issue:
Description:ORR is a proportion of patients with a best overall response defined as complete response or partial response by RECIST1.1

Secondary Outcome Measures

Measure:Duration of response
Time Frame:At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months
Safety Issue:
Description:DOR is calculated as the time from the date of the first document of complete remission (CR) or partial remission (PR) to the first documented preogressive disease (PD) or death due to any cause for patients with PR or CR.
Measure:Progression-free survival
Time Frame:At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months
Safety Issue:
Description:. PFS is defined as time from the first dose of investigational products (IPs) to progression or death due to any cause. OS is defined as time from the first dose of IPs to death due to any cause.
Measure:Overall survival
Time Frame:At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months
Safety Issue:
Description:DCR is calculated as the proportion of patients with best response of CR, PR and SD.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Asan Medical Center

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