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

NCT02672358 | Withdrawn Phase 2

• 1 other identifier: CDRB436E1201
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Non-Small-Cell Lung Cancer

Keywords

Non-Small-Cell Lung Cancer; NSCLC; dabrafenib; trametinib; Japanese patients; BRAF V600E mutation positive metastatic; stage IV

Outcome Measures

Primary Outcomes (1)

• 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

  Approximately 2 years

Secondary Outcomes (4)

• Duration of response (DOR)

  Approximately 2 years

• Disease control rate (DCR)

  Approximately 2 years

• Progression-free survival (PFS)

  Approximately 2 years

• Overall survival (OS)

  Approximately 2 years

Study Arms (1)

Dabrafenib +Trametinib

EXPERIMENTAL

Oral Dabrafenib plus Oral Trametinib

Drug: Dabrafenib; Drug: Trametinib

Interventions

Dabrafenib DRUG

Oral Dabrafenib 150 mg BID

Dabrafenib +Trametinib

Trametinib DRUG

Oral Trametinib 2 mg QD

Dabrafenib +Trametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 3, 2016
• Study Start: September 3, 2018
• Primary Completion: September 2, 2019
• Study Completion: December 7, 2020
• Last Updated: August 10, 2018

Record last verified: 2018-08