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.
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
| Drug | Synonyms | Arms |
|---|
| Dabrafenib | | Dabrafenib +Trametinib |
| Trametinib | | Dabrafenib +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
| Name | Type | Description | Interventions |
|---|
| Dabrafenib +Trametinib | Experimental | Oral Dabrafenib plus Oral 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: | Withdrawn |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Non-Small-Cell Lung Cancer
- NSCLC
- dabrafenib
- trametinib
- Japanese patients
- BRAF V600E mutation positive metastatic
- stage IV
Last Updated
August 10, 2018
