A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01584648
First received: April 23, 2012
Last updated: August 28, 2014
Last verified: August 2014
Results First Received: April 10, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Drug: dabrafenib
Drug: dabrafenib plus trametinib placebo
Drug: 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
Participants (par.) with advanced or metastatic (Stage IIIc or Stage IV) BRAF V600E/K mutation-positive melanoma were enrolled in this randomized, double-blinded, multi-center Phase III study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Dabrafenib + Trametinib Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Dabrafenib + Placebo Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.

Participant Flow:   Overall Study
    Dabrafenib + Trametinib     Dabrafenib + Placebo  
STARTED     211     212  
Ongoing     154     147  
COMPLETED     0     0  
NOT COMPLETED     211     212  
Lost to Follow-up                 4                 3  
Physician Decision                 2                 2  
Withdrawal by Subject                 11                 5  
Death                 40                 55  
Ongoing                 154                 147  



  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.
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Reporting Groups
  Description
Dabrafenib + Trametinib Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Dabrafenib + Placebo Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Total Total of all reporting groups

Baseline Measures
    Dabrafenib + Trametinib     Dabrafenib + Placebo     Total  
Number of Participants  
[units: participants]
  211     212     423  
Age  
[units: Years]
Mean ± Standard Deviation
  55.1  ± 13.33     55.3  ± 13.75     55.2  ± 13.52  
Gender  
[units: Participants]
     
Female     100     98     198  
Male     111     114     225  
Race/Ethnicity, Customized  
[units: Participants]
     
African American/African Heritage     0     1     1  
White - White/Caucasian/European Heritage     211     211     422  



  Outcome Measures
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1.  Primary:   Progression-Free Survival (PFS) as Assessed by the Investigator   [ Time Frame: From randomization until the earliest date of disease progression (PD) or death due to any cause (average of 9 study months) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: From randomization until death due to any cause (average of 9 study months) ]

3.  Secondary:   Number of Participants With a Confirmed Response (Complete Response or Partial Response)   [ Time Frame: From randomization until the first documented complete response or partial response (average of 9 study months) ]

4.  Secondary:   Duration of Response for Participants With a Confirmed Response (Complete Response or Partial Response)   [ Time Frame: From the time of the first documented response (CR or PR) until disease progression (average of 9 study months) ]

5.  Secondary:   Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)   [ Time Frame: From the time the first dose of study treatment administered until 30 days after discontinuation of study treatment (average of 9 study months) ]

6.  Secondary:   Number of Participants With a Worst-case On-therapy Grade Change From Baseline to Grade 3 and 4 for the Indicated Clinical Chemistry Parameters   [ Time Frame: From Baseline up to Week 64 ]

7.  Secondary:   Number of Participants With a Worst-case On-therapy Grade Change From Baseline to Grade 3 and 4 for the Indicated Hematology Parameters   [ Time Frame: From Baseline up to Week 64 ]

8.  Secondary:   Number of Participants With a Worst-case On-therapy Change From Baseline With Respect to the Normal Range for the Indicated Hematology Parameters   [ Time Frame: From Baseline up to Week 64 ]

9.  Secondary:   Number of Participants With a Worst-case On-therapy Change From Baseline With Respect to the Normal Range for the Indicated Clinical Chemistry Parameters   [ Time Frame: From Baseline up to Week 64 ]

10.  Secondary:   Number of Participants With a Worst-case On-therapy Change From Baseline in Heart Rate   [ Time Frame: From Baseline up to Week 64 ]

11.  Secondary:   Number of Participants With a Worst-case On-therapy Change From Baseline in Systolic and Diastolic Blood Pressure to Grade 2 or Grade 3   [ Time Frame: From Baseline up to Week 64 ]

12.  Secondary:   Number of Participants With a Worst-case On-therapy Change From Baseline in Temperature   [ Time Frame: From Baseline up to Week 64 ]

13.  Secondary:   Number of Participants With a Worse-case On-therapy Change From Baseline in the Bazett's QTc to Grade 2 or Grade 3   [ Time Frame: From Baseline up to Week 60 ]

14.  Secondary:   Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram   [ Time Frame: From Baseline up to Week 60 ]

15.  Secondary:   Number of Participants With Incidence of Squamous Cell Carcinoma   [ Time Frame: From Baseline up to end of study (average of 9 study months) ]

16.  Secondary:   Plasma Concentrations of Trametinib   [ Time Frame: Week 8: pre-dose, 1-3 hours and 4-6 hours post dose; Week 16 pre-dose and Week 24 pre-dose ]

17.  Secondary:   Plasma Concentrations of Dabrafenib and Its Metabolites   [ Time Frame: Week 8: pre-dose, 1-3 hours and 4-6 hours post dose; Week 16 pre-dose and Week 24 pre-dose ]


  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: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01584648     History of Changes
Other Study ID Numbers: 115306
Study First Received: April 23, 2012
Results First Received: April 10, 2014
Last Updated: August 28, 2014
Health Authority: Australia: Human Research Ethics Committee
United States: Food and Drug Administration
Canada: Health Canada