Clinical trial NCT02672358: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Non-Small-Cell Lung Cancer
Keywords: Non-Small-Cell Lung Cancer
NSCLC
dabrafenib
trametinib
Japanese patients
BRAF V600E mutation positive metastatic
stage IV
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-02-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall Response Rate (ORR) by investigator assessment
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: Approximately 2 years
measure: Disease control rate (DCR)
timeFrame: Approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Approximately 2 years
measure: Overall survival (OS)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: