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Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer.

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01336634
First Posted: April 18, 2011
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
Results First Submitted: October 5, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Cancer
Interventions: Drug: Dabrafenib
Device: Trametinib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Eligible participants (par.) were enrolled in Cohort (Coh) A (monotherapy [Dabrafenib{DAB}]). Par. in Coh-A who had disease progression and adequately tolerating DAB were given option to crossover to Coh-B who received combination therapy (DAB+Trametinib). In Coh-C, par. without prior anti-cancer treatment received combination therapy.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Par. with metastatic non-small cell lung cancer (NSCLC) were screened and allocated to Coh-A (DAB twice daily [BID] i.e. monotherapy), Coh-B (Combination Second-Line Plus) and Coh-C (Combination First-Line) according to their eligibility. The results presented are based on the Interim Analysis.

Reporting Groups
  Description
Monotherapy All Treated Participants with or without prior systemic anti-cancer therapy received dabrafenib 150 mg BID. It was continued until disease progression or death or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.
Combination Second-Line Plus Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received dabrafenib 150 mg BID and trametinib 2 mg once daily (OD). It was continued until disease progression or death or unacceptable AEs or investigator discretion to discontinue.
Combination First-Line Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given dabrafenib 150 mg BID and trametinib 2 mg OD. It was continued until disease progression or death or unacceptable AEs or at investigator discretion to discontinue.

Participant Flow:   Overall Study
    Monotherapy All Treated   Combination Second-Line Plus   Combination First-Line
STARTED   84   57   36 
COMPLETED   0   0   0 
NOT COMPLETED   84   57   36 
Death                60                33                10 
Lost to Follow-up                2                1                1 
Withdrawal by Subject                6                0                1 
Physician Decision                1                1                0 
Ongoing                15                22                24 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Monotherapy All Treated Participants with or without prior systemic anti-cancer therapy received dabrafenib 150 mg BID. It was continued until disease progression or death or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.
Combination Second-Line Plus Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received dabrafenib 150 mg BID and trametinib 2 mg once daily (OD). It was continued until disease progression or death or unacceptable AEs or investigator discretion to discontinue.
Combination First-Line Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given dabrafenib 150 mg BID and trametinib 2 mg OD. It was continued until disease progression or death or unacceptable AEs or at investigator discretion to discontinue.
Total Total of all reporting groups

Baseline Measures
   Monotherapy All Treated   Combination Second-Line Plus   Combination First-Line   Total 
Overall Participants Analyzed 
[Units: Participants]
 84   57   36   177 
Age 
[Units: Years]
Mean (Standard Deviation)
 64.8  (10.51)   65.1  (10.14)   67.8  (11.00)   65.5  (10.50) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      44  52.4%      28  49.1%      22  61.1%      94  53.1% 
Male      40  47.6%      29  50.9%      14  38.9%      83  46.9% 
Race/Ethnicity, Customized 
[Units: Participants]
       
Asian - East Asian Heritage   14   3   3   20 
Asian - Central/South Asian Heritage   2   0   0   2 
Asian - Japanese Heritage   2   1   0   3 
African American/African Heritage   2   2   1   5 
Native Hawaiian Or Other Pacific Islander   0   0   1   1 
White - Arabic/North African Heritage   2   2   0   4 
White - White/Caucasian/European Heritage   62   47   30   139 
Other-African American/African Heritage   0   1   0   1 
Other-missing   0   1   1   2 


  Outcome Measures
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1.  Primary:   Percentage of Participants With Overall Response Rate (ORR) at the Date of Analysis   [ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months ]

2.  Secondary:   Duration of Response (DoR) at the Date of Analysis   [ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months ]

3.  Secondary:   Progression Free Survival (PFS) at the Date of Analysis   [ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months ]

4.  Secondary:   Overall Survival (OS) at the Date of Analysis   [ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months ]

5.  Secondary:   Number of Participants With Abnormal Vital Signs Values   [ Time Frame: Up to Week 12 and then every 3 weeks until discharge, for an average of 13.8 months ]

6.  Secondary:   Number of Participants With Abnormal Electrocardiogram (ECG) Values   [ Time Frame: Week 3, Week 6, Week 15 and then every 9 weeks until discharge, for an average of 13.8 months ]

7.  Secondary:   Number of Participants With Abnormal Echocardiogram Findings   [ Time Frame: Week 6, Week 15 and then every 9 weeks until discharge, for an average of 13.8 months ]

8.  Secondary:   Number of Participants With Abnormal Clinical Chemistry Values   [ Time Frame: Up to Week 12 and then every 3 weeks until discharge, for an average of 13.8 months ]

9.  Secondary:   Number of Participants With Abnormal Hematology Values   [ Time Frame: Up to Week 12 and then every 3 weeks until discharge, for an average of 13.8 months ]

10.  Secondary:   Number of Participants With AEs and Serious AEs (SAEs)   [ Time Frame: Up to Week 12 and then every 3 weeks up to follow up, for an average of 13.8 months ]

11.  Secondary:   Apparent Clearance (CL/F) of Dabrafenib and Trametinib   [ Time Frame: Week 3, Week 6, Week 12 and Week 18 ]

12.  Secondary:   Volume of Distribution (V/F) of Dabrafenib and Trametinib   [ Time Frame: Week 3, Week 6, Week 12 and Week 18 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: Novartis.email@novartis.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01336634     History of Changes
Other Study ID Numbers: 113928
First Submitted: April 7, 2011
First Posted: April 18, 2011
Results First Submitted: October 5, 2016
Results First Posted: December 7, 2017
Last Update Posted: December 7, 2017