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Withdrawn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
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
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
NCT ID
NCT02672358
First Posted
February 1, 2016
Last Updated
August 8, 2018
Sponsor
Novartis Pharmaceuticals
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
We'll reach out to this number within 24 hrs