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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02672358

Collaborator

(none)

Enrollment

Arm

27.1

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small-Cell Lung Cancer	Drug: Dabrafenib Drug: Trametinib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 3, 2018

Anticipated Primary Completion Date :

Sep 2, 2019

Anticipated Study Completion Date :

Dec 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dabrafenib +Trametinib Oral Dabrafenib plus Oral Trametinib	Drug: Dabrafenib Oral Dabrafenib 150 mg BID Drug: Trametinib Oral Trametinib 2 mg QD

Arm

Intervention/Treatment

Experimental: Dabrafenib +Trametinib

Oral Dabrafenib plus Oral Trametinib

Drug: Dabrafenib

Oral Dabrafenib 150 mg BID

Drug: Trametinib

Oral Trametinib 2 mg QD

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) by investigator assessment [Approximately 2 years]
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) [Approximately 2 years]
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) [Approximately 2 years]
DCR, defined as the proportion of patients with best overall response of CR, PR, or SD.
Progression-free survival (PFS) [Approximately 2 years]
PFS, defined as the interval between first dose and the earliest date of disease progression or death due to any cause.
Overall survival (OS) [Approximately 2 years]
OS, defined as the time from the date of first dose until death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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