A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma to the Brain (Break MB)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01266967
First received: December 2, 2010
Last updated: April 24, 2014
Last verified: March 2014
Results First Received: June 24, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Melanoma and Brain Metastases
Intervention: Drug: GSK2118436

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
GSK2118436 150 mg: No Prior Local Therapy Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
GSK2118436 150 mg: Prior Local Therapy Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.

Participant Flow:   Overall Study
    GSK2118436 150 mg: No Prior Local Therapy     GSK2118436 150 mg: Prior Local Therapy  
STARTED     89     83  
COMPLETED     0     0  
NOT COMPLETED     89     83  
Death                 69                 61  
Study Closed/Terminated                 15                 17  
Lost to Follow-up                 2                 1  
Physician Decision                 0                 1  
Withdrawal by Subject                 3                 3  



  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
GSK2118436 150 mg: No Prior Local Therapy Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
GSK2118436 150 mg: Prior Local Therapy Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Total Total of all reporting groups

Baseline Measures
    GSK2118436 150 mg: No Prior Local Therapy     GSK2118436 150 mg: Prior Local Therapy     Total  
Number of Participants  
[units: participants]
  89     83     172  
Age  
[units: Years]
Mean ± Standard Deviation
  52.3  ± 13.35     52.7  ± 13.83     52.5  ± 13.55  
Gender  
[units: Participants]
     
Female     24     28     52  
Male     65     55     120  
Race/Ethnicity, Customized [1]
[units: participants]
     
White     89     82     171  
Not reported     0     1     1  
[1] Race was not reported for one participant who recevied prior local therapy.



  Outcome Measures
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1.  Primary:   Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator   [ Time Frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 18.3 weeks) ]

2.  Secondary:   Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator   [ Time Frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 24 weeks) ]

3.  Secondary:   Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator   [ Time Frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 17 weeks) ]

4.  Secondary:   Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator   [ Time Frame: From the time of the Baseline assessment until disease progression or end of study treatment (average of 16 weeks) ]

5.  Secondary:   Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants   [ Time Frame: Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 27 weeks) ]

6.  Secondary:   Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants   [ Time Frame: Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 31 weeks) ]

7.  Secondary:   Duration of Overall Response for the Subset of V600E Mutation-positive Participants   [ Time Frame: Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 28 weeks) ]

8.  Secondary:   Duration of Overall Response for the Subset of V600K Mutation-positive Participants   [ Time Frame: Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 31 weeks) ]

9.  Secondary:   Progression-free Survival in V600E Mutation-positive Participants   [ Time Frame: Time from the first dose of study medication to the earliest of death or progression (average of 23 weeks) ]

10.  Secondary:   Progression-free Survival in V600K Mutation-positive Participants   [ Time Frame: Time from the first dose of study medication to the earliest of death or progression (average of 17 weeks) ]

11.  Secondary:   Overall Survival of V600E Mutation-positive Participants   [ Time Frame: Time from the first dose of study medication until death due to any cause (average of 35 weeks) ]

12.  Secondary:   Overall Survival in V600K Mutation-positive Participants   [ Time Frame: Time from the first dose of study medication until death due to any cause (average of 26 weeks) ]

13.  Secondary:   Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)   [ Time Frame: From Screening until the conclusion of the study (up to 103 weeks) ]

14.  Secondary:   Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters   [ Time Frame: From Screening until the conclusion of the study (up to 103 weeks) ]

15.  Secondary:   Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities   [ Time Frame: From Screening until the conclusion of the study (up to 103 weeks) ]

16.  Secondary:   Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters   [ Time Frame: From Screening until the conclusion of the study (up to 103 weeks) ]

17.  Secondary:   Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36   [ Time Frame: Baseline; Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 ]

18.  Secondary:   Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG)   [ Time Frame: Baseline; Weeks 4, 12, 20, 28, 40, 52, and 64 ]

19.  Secondary:   Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12   [ Time Frame: Weeks (W) 4 and 12 ]

20.  Secondary:   Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542   [ Time Frame: Week 4 (pre-dose and 1-3 hours post-dose) and Weeks 8, 16, 24, and 32 (either pre-dose in the morning or in the afternoon at 4-8 hours post-dose) ]

21.  Secondary:   Composite of Pharmacokinetic Parameters of GSK2118436 in a Subset of Participants Receiving Dexamethasone   [ Time Frame: Day 15 ]

22.  Secondary:   Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response   [ Time Frame: Screening ]


  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: NCT01266967     History of Changes
Other Study ID Numbers: 113929
Study First Received: December 2, 2010
Results First Received: June 24, 2013
Last Updated: April 24, 2014
Health Authority: Italy: Agenzia Italiana del Farmaco
United States: Food and Drug Administration
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
France: Agence Française de Sécurité Sanitaire des Produits de Santé
European Union: European Medicines Agency
Canada: Health Canada
Australia: Therapeutic Goods Administration