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A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma

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ClinicalTrials.gov Identifier: NCT01227889
Recruitment Status : Completed
First Posted : October 25, 2010
Results First Posted : May 16, 2014
Last Update Posted : October 4, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Cancer
Interventions: Drug: GSK2118436
Drug: Dacarbazine (DTIC)

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This was a Phase III randomized, open-label study to compare GSK2118436 to Dacarbazine (DTIC) in previously untreated participants (par.) with BRAF mutation positive advanced (Stage III) or metastatic (Stage IV) melanoma. This study was conducted at 70 centers in 12 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study has 2 phases: Randomized and Crossover Phase. In Randomized Phase, a total of 250 par. were randomized in 3:1 to receive either oral dabrafenib 150 mg twice daily (BID) or intravenous DTIC 1000 milligram/meter square. Par. in DTIC arm with disease progression were considered for crossover to dabrafenib arm in Crossover Phase

Reporting Groups
  Description
GSK2118436 150 mg BID Participants (par.) were randomly assigned to receive oral GSK2118436 150 milligrams (mg) twice a day (BID). Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until disease progression (DP), death, the occurrence of an unacceptable adverse event (AE), or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase In the RP, par. received intravenous (IV) Dacarbazine (DTIC) 1000 mg per meters squared (mg/m^2) every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Par. continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Par. who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Par. who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover par. continued on GSK2118436 until further DP was noted. After DP on GSK2118436, par. were followed for response, progression, survival, and further anti-cancer therapy.

Participant Flow for 2 periods

 Period 1:   Randomized Phase (RP)
    GSK2118436 150 mg BID   DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase
STARTED   187   63 
COMPLETED   0   0 
NOT COMPLETED   187   63 
Adverse Event                13                0 
Physician Decision                13                5 
Progressive Disease                135                52 
Study terminated by sponsor                10                0 
Missing                1                3 
Withdrawal by Subject                15                3 

Period 2:   Crossover Phase
    GSK2118436 150 mg BID   DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase
STARTED   0   37 [1] 
COMPLETED   0   0 
NOT COMPLETED   0   37 
Adverse Event                0                1 
Physician Decision                0                3 
Progressive Disease                0                31 
Study Terminated By Sponsor                0                1 
Withdrawal by Subject                0                1 
[1] As of the data cut on December 18, 2012, 36 of 63 participants crossed over from DTIC to GSK2118436.



  Baseline Characteristics

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
GSK2118436 150 mg BID Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase In the RP, par. received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Par. continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Par. who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Par. who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover par. continued on GSK2118436 until further DP was noted. After DP on GSK2118436, par. were followed for response, progression, survival, and further anti-cancer therapy.
Total Total of all reporting groups

Baseline Measures
   GSK2118436 150 mg BID   DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 187   63   250 
Age 
[Units: Years]
Mean (Standard Deviation) 		 53.5  (13.76)   51.6  (14.22)   53.0  (13.87) 
Sex: Female, Male 
[Units: Participants]
Count of Participants 		     
Female      75  40.1%      26  41.3%      101  40.4% 
Male      112  59.9%      37  58.7%      149  59.6% 
Race/Ethnicity, Customized 
[Units: Participants]
 		     
White   186   63   249 
Missing   1   0   1 


  Outcome Measures

1.  Primary:   Progression-free Survival (PFS) as Assessed by the Investigator   [ Time Frame: Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months) ]
  Show Outcome Measure 1

2.  Primary:   Progression-free Survival (PFS) as Assessed by an Independent Radiologist: Randomized Phase   [ Time Frame: Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months) ]
  Show Outcome Measure 2

3.  Secondary:   Overall Survival   [ Time Frame: Time interval between the date of randomization and the date of death due to any cause (up to 22.1 months) ]
  Show Outcome Measure 3

4.  Secondary:   Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Randomized Phase   [ Time Frame: From randomization until the first documented evidence of a confirmed complete response or partial response (median of 6.6 weeks) ]
  Show Outcome Measure 4

5.  Secondary:   Number of Participants With a Best Overall Response of Confirmed CR or PR as Assessed by an Independent Radiologist: Randomized Phase   [ Time Frame: From randomization until the first documented evidence of a confirmed complete response or partial response (median of 12.0 weeks) ]
  Show Outcome Measure 5

6.  Secondary:   Duration of Response as Assessed by the Investigator: Randomized Phase   [ Time Frame: Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 65.6 weeks) ]
  Show Outcome Measure 6

7.  Secondary:   Duration of Response as Assessed by an Independent Radiologist: Randomized Phase   [ Time Frame: Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 7.4 months) ]
  Show Outcome Measure 7

8.  Secondary:   Progression-free Survival (PFS2) as Assessed by the Investigator: Crossover Phase   [ Time Frame: Time from first dose of GSK2118436 in participants who crossover after initial progression to the earliest date of radiographical or photographical PD or death due to any cause (up to 6.4 months) ]
  Show Outcome Measure 8

9.  Secondary:   Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Crossover Phase   [ Time Frame: From randomization until the first documented evidence of a confirmed complete response or partial response (up to 6.4 months) ]
  Show Outcome Measure 9

10.  Secondary:   Duration of Response as Assessed by the Investigator: Crossover Phase   [ Time Frame: Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 6.4 months) ]
  Show Outcome Measure 10

11.  Secondary:   Number of Participants With Non-melanoma Skin Lesions: Randomized Phase   [ Time Frame: From Screening until study completion or discontinuation from the study (up to 9.9 months) ]
  Show Outcome Measure 11

12.  Secondary:   Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay   [ Time Frame: Screening ]
  Show Outcome Measure 12


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information

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:

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


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01227889     History of Changes
Other Study ID Numbers: 113683
First Submitted: October 21, 2010
First Posted: October 25, 2010
Results First Submitted: June 6, 2013
Results First Posted: May 16, 2014
Last Update Posted: October 4, 2017