GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01245062
First received: November 18, 2010
Last updated: October 17, 2013
Last verified: October 2013
Results First Received: February 14, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Drug: GSK1120212
Drug: Chemotherapy

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants (par.) were stratified for lactate dehydrogenase and prior chemotherapy (CT) for advanced or metastatic disease. Par. in each stratum were randomized in a 2:1 ratio to receive either trametinib or CT until disease progression, death, or withdrawal. Par. randomized to CT were allowed to cross-over to trametinib.

Reporting Groups
  Description
Trametinib Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signalling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 mg tablet once daily until disease progression, death, or withdrawal.
Chemotherapy Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Cross-over From Chemotherapy to Trametinib Following independent review confirmation of disease progression, participants randomized to chemotherapy were allowed to cross-over to Trametinib.

Participant Flow for 2 periods

Period 1:   Randomization Phase
    Trametinib     Chemotherapy     Cross-over From Chemotherapy to Trametinib  
STARTED     214     108     0  
Ongoing     169     65     0  
COMPLETED     0     0     0  
NOT COMPLETED     214     108     0  
Death                 35                 29                 0  
Lost to Follow-up                 2                 1                 0  
Physician Decision                 2                 3                 0  
Withdrew Consent                 6                 10                 0  
Ongoing                 169                 65                 0  

Period 2:   Cross-over Phase
    Trametinib     Chemotherapy     Cross-over From Chemotherapy to Trametinib  
STARTED     0     0     51 [1]
Ongoing     0     0     34  
COMPLETED     0     0     0  
NOT COMPLETED     0     0     51  
Death                 0                 0                 14  
Withdrew Consent                 0                 0                 3  
Ongoing                 0                 0                 34  
[1] 51 of the 108 participants randomized to chemotherapy elected to cross-over to Trametinib.



  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
Trametinib Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signalling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 mg tablet once daily until disease progression, death, or withdrawal.
Chemotherapy Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Total Total of all reporting groups

Baseline Measures
    Trametinib     Chemotherapy     Total  
Number of Participants  
[units: participants]
  214     108     322  
Age  
[units: Years]
Mean ± Standard Deviation
  54.3  ± 12.97     52.8  ± 13.56     53.8  ± 13.17  
Gender  
[units: Participants]
     
Female     94     55     149  
Male     120     53     173  
Race/Ethnicity, Customized  
[units: Participants]
     
White - Arabic/North African Heritage     2     0     2  
White - White/Caucasian/European Heritage     212     107     319  
White - Mixed Race     0     1     1  



  Outcome Measures
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1.  Primary:   Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

2.  Secondary:   Progression-free Survival in All Participants   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

3.  Secondary:   PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

4.  Secondary:   PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

5.  Secondary:   Overall Survival in All Participants   [ Time Frame: Day 1 until death due to any cause (average of 4.8 months) ]

6.  Secondary:   Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases   [ Time Frame: Day 1 until death due to any cause (average of 4.8 months) ]

7.  Secondary:   Number of BRAF V600E Mutation-positive Participants Without a History of Brain Metastases With Overall Response (OR) as Assessed by the Investigator and Independent Review   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

8.  Secondary:   Number of Participants With OR as Assessed by the Investigator and Independent Review   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

9.  Secondary:   Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

10.  Secondary:   Number of BRAF V600K Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

11.  Secondary:   Number of Participants With OR Following Cross-over to Trametinib   [ Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 2.72 months) ]

12.  Secondary:   Duration of Response (DR) for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classifed as Confirmed Responders (CR or PR) as Assessed by the Investigator and Independent Review   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

13.  Secondary:   DR for All Confirmed Responders (CR or PR) as Assessed by the Investigator or Independent Review   [ Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 4.8 months) ]

14.  Secondary:   DR for All Responders (CR or PR) Following Cross-over to Trametinib as Assessed by the Investigator   [ Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 2.72 months) ]

15.  Secondary:   PFS Following Cross-over to Trametinib as Assessed by the Investigator   [ Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 2.72 months) ]


  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


Publications of Results:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01245062     History of Changes
Other Study ID Numbers: 114267
Study First Received: November 18, 2010
Results First Received: February 14, 2013
Last Updated: October 17, 2013
Health Authority: Australia: Human Research Ethics Committee
United States: Food and Drug Administration
Canada: Health Canada