A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma

• ClinicalTrials.gov Identifier: NCT01153763
• Recruitment Status: Completed
• First Posted: June 30, 2010
• Results First Posted: June 2, 2014
• Last Update Posted: September 27, 2017
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma
• Intervention: Drug: GSK2118436
• Enrollment: 92

Participant Flow

Recruitment Details	Eligible participants received Dabrafenib (GSK2118436) 150 milligram (mg) twice daily and continued on treatment until disease progression, death, unacceptable adverse event (AE), or early termination of the study. The total duration of the study including a long-term follow-up phase was 5 years.
Pre-assignment Details	A total of 211 participants with histologically confirmed BRAF mutation positive metastatic melanoma (Stage IV) were screened for eligibility. 152 participants had a BRAF V600E or V600K mutation and 92 participants with positive mutation were included in the study.

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Period Title: Overall Study
Started	92
Completed	71
Not Completed	21
Reason Not Completed
Study Closed	16
Lost to Follow-up	1
Physician Decision	2
Withdrawal by Subject	2

Baseline Characteristics

Arm/Group Title		GSK2118436 150 mg
Arm/Group Description		Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Baseline Participants		92
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	92 participants
		54.8 (14.44)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	92 participants
	Female	43 46.7%
	Male	49 53.3%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	92 participants
White		91
American Indian or Alaska Native		1

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator for Participants Who Had a BRAF V600E Mutation
Description	A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeter (mm) in the short axis.) or PR (at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment was required at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later were required to be confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. The analysis was performed on Primary efficacy Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600E mutation.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Primary efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	76
Measure Type: Number; Unit of Measure: Participants
CR	5
PR	40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK2118436 150 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	59
	Confidence Interval	(2-Sided) 95%; 48.2 to 70.3
	Estimation Comments	The estimated value represents the percentage of participants with a confirmed CR or a confirmed PR.

2. Secondary Outcome

Title	Number of Participants With a Best Overall Response of CR or PR as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
Description	A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment had to have been performed at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later should have been confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. The analysis was performed on Secondary efficacy analysis Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600K mutation.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Secondary Efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	16
Measure Type: Number; Unit of Measure: Participants
Investigator-assessed CR	0
Investigator-assessed PR	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK2118436 150 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	13
	Confidence Interval	(2-Sided) 95%; 0.0 to 28.7
	Estimation Comments	The estimated value represents the percentage of participants with a investigator assessed CR or PR.

3. Secondary Outcome

Title	Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation
Description	PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or progression minus date of first dose plus 1 day. Kaplan-Meier model was used to estimate the median and 95 percent confidence interval (CI). For participants who received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was censored at the last adequate assessment. For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	76
Median (95% Confidence Interval); Unit of Measure: Weeks
	6.3; (4.6 to 8.1)

4. Secondary Outcome

Title	Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
Description	PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or progression minus date of first dose plus 1 day. Kaplan-Meier model was used to estimate the median and 95 percent CI. For participants who received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was censored at the last adequate assessment. For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Secondary Efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	16
Median (95% Confidence Interval); Unit of Measure: Weeks
	4.0; (2.6 to 6.2)

5. Secondary Outcome

Title	Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation
Description	Duration of response for participants with either a CR or PR is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. Duration of response was estimated using Kaplan-Meier model and the median and 95 percent CI was presented. The analysis was performed on Primary efficacy Population and only those participants who had a CR or PR were analyzed.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	45
Median (95% Confidence Interval); Unit of Measure: Weeks
	6.6; (3.9 to 11.1)

6. Secondary Outcome

Title	Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
Description	Duration of response for participants with either a CR or PR is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. Duration of response was estimated using Kaplan-Meier model and the median and 95 percent CI was presented. The analysis was performed on Secondary efficacy Population and only those participants who had a CR or PR were analyzed.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Secondary Efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	3
Median (95% Confidence Interval); Unit of Measure: Weeks
	5.6; (3.7 to 6.8)

7. Secondary Outcome

Title	Overall Survival for Participants Who Had a BRAF V600E Mutation
Description	Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. Overall survival was estimated using kaplan-Meier model and median and 95 percent CI was presented.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	76
Median (95% Confidence Interval); Unit of Measure: Weeks
	13.1; (9.5 to 21.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK2118436 150 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	20
	Confidence Interval	(2-Sided) 95%; 11.6 to 29.8
	Estimation Comments	The estimated value represents the percentage of participants with overall survival.

8. Secondary Outcome

Title	Overall Survival for Participants Who Had a BRAF V600K Mutation
Description	Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. Overall survival was estimated using Kaplan-Meier model and median and 95 percent CI was presented.
Time Frame	From the first dose to death due to any cause (up to 60 months)

Outcome Measure Data

Analysis Population Description

Secondary Efficacy Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	16
Median (95% Confidence Interval); Unit of Measure: Weeks
	12.9; (4.2 to 17.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK2118436 150 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	13
	Confidence Interval	(2-Sided) 95%; 2.2 to 34.6
	Estimation Comments	The estimated value represents the percentage of participants with overall survival.

9. Secondary Outcome

Title	Number of Participants With AEs and Serious Adverse Events (SAEs)
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs including systemic allergic and non-allergic reactions as well as local site injection-related reactions were counted throughout treatment phase and follow up phase. Systemic allergic reactions included facial paralysis, flushing, hypersensitivity and rash pruritic. Injection related reactions were considered as systemic non-allergic reactions. Local site reactions included injection site bruising, erythema, pain and reaction. The analysis was performed on All treated Population which comprised of all participants that receive at least one dose of dabrafenib.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

All treated Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	92
Measure Type: Number; Unit of Measure: Participants
Any AE	87
Any SAE	33

10. Secondary Outcome

Title	Number of Participants With Change From Baseline in Clinical Chemistry and Hematology Toxicity Grades
Description	Blood samples were collected from participants for evaluation of change from Baseline in toxicity grades in clinical chemistry and hematology parameters. The clinical chemistry parameters included alkaline phosphatase, Alanine amino transferase (ALT), Aspartate amino transferase (AST), total bilirubin, creatinine, glucose, potassium, magnesium, sodium and phosphorus. The hematology parameters included hemoglobin, total neutrophils, platelets and white blood cells (WBC). Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst case post-baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

All treated Population

Arm/Group Title		GSK2118436 150 mg
Arm/Group Description:		Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed		92
Measure Type: Number; Unit of Measure: Participants
Alkaline phosphatase; n= 91	Number Analyzed	91 participants
		23
ALT; n= 91	Number Analyzed	91 participants
		18
AST; n= 91	Number Analyzed	91 participants
		18
Total bilirubin; n= 91	Number Analyzed	91 participants
		3
Creatinine; n= 91	Number Analyzed	91 participants
		11
Glucose; n= 90	Number Analyzed	90 participants
		51
Potassium; n= 91	Number Analyzed	91 participants
		2
Magnesium; n= 89	Number Analyzed	89 participants
		2
Sodium; n= 91	Number Analyzed	91 participants
		5
Phosphorus; n= 91	Number Analyzed	91 participants
		36
Hemoglobin; n= 91	Number Analyzed	91 participants
		0
Total Neutrophils; n= 91	Number Analyzed	91 participants
		21
Platelet; n= 91	Number Analyzed	91 participants
		12
WBC; n= 91	Number Analyzed	91 participants
		24

11. Secondary Outcome

Title	Number of Participants With Change From Baseline in Temperature and Pulse Rate
Description	Number of participants with change from Baseline in temperature and pulse rate were evaluated from the first dose of study treatment till discontinuation due to any reason. Change from Baseline in worst-case post Baseline value was presented as decrease to <=35, change to normal or no change and increase to >=38. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst case post-baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

All treated Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	91
Measure Type: Number; Unit of Measure: Participants
Temperature; Decrease to <=35	3
Temperature; Change to normal or no change	84
Temperature; Increase to >=38	4
Pulse rate; Decrease to <=35	9
Pulse rate; Change to normal or no change	66
Pulse rate; Increase to >=38	16

12. Secondary Outcome

Title	Number of Participants With Increase From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description	Number of participants with increase from Baseline in SBP and DBP were evaluated from the first dose of study treatment till discontinuation due to any reason. Change from Baseline in worst-case post Baseline value was presented as any increase to >=80 and increase to >=100 for DBP and as any increase to >=120 and increase to >=160 for SBP. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst-case post Baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period. One participant out of the 92 participants (76 BRAF V600E patients + 16 BRAF V600K patients) did not have SBP and DBP collected after baseline.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

All treated Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	91
Measure Type: Number; Unit of Measure: Participants
DBP; Any increase to >=80	32
DBP; Increase to >=100	6
SBP; Any icrease to >=120	2
SBP; Increase to >=160	7

13. Secondary Outcome

Title	Number of Participants With Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Levels
Description	LVEF was defined as the percentage of blood pumped out of the left ventricle. Change from Baseline in worst-case post Baseline was presented as no change or any increase and any decrease values. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst-case post Baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

All treated Population

Arm/Group Title	GSK2118436 150 mg
Arm/Group Description:	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
Overall Number of Participants Analyzed	92
Measure Type: Number; Unit of Measure: Participants
No change or any increase	34
Any decrease	54

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product until death of all participants or a follow-up till 60 months.
Adverse Event Reporting Description	SAEs and non-serious AEs were collected in the All Treated Participants Population, comprised of all randomized participants who received at least one dose of study medication, according to the actual treatment received.
Arm/Group Title	GSK2118436 150 mg
Arm/Group Description	Participants received GSK2118436 (gelatin capsules) 150 mg orally twice a day and continued on treatment until disease progression, death, or unacceptable AEs . Participants who are benefiting from GSK2118436 at the time of study completion will have the option to enter Study BRF114144 (NCT01231594), which is a rollover study for GSK2118436.
All-Cause Mortality
	GSK2118436 150 mg
	Affected / at Risk (%)
Total	71/92 (77.17%)
Serious Adverse Events
	GSK2118436 150 mg
	Affected / at Risk (%)
Total	33/92 (35.87%)
Blood and lymphatic system disorders
Anaemia † 1	2/92 (2.17%)
Thrombocytopenia † 1	1/92 (1.09%)
Cardiac disorders
Arrhythmia supraventricular † 1	1/92 (1.09%)
Atrial fibrillation † 1	1/92 (1.09%)
Atrial flutter † 1	1/92 (1.09%)
Endocrine disorders
Hypothyroidism † 1	1/92 (1.09%)
Gastrointestinal disorders
Intestinal obstruction † 1	1/92 (1.09%)
Nausea † 1	1/92 (1.09%)
Vomiting † 1	3/92 (3.26%)
General disorders
Adverse drug reaction † 1	1/92 (1.09%)
Chills † 1	1/92 (1.09%)
Non-cardiac chest pain † 1	2/92 (2.17%)
Pyrexia † 1	4/92 (4.35%)
Infections and infestations
Appendicitis † 1	1/92 (1.09%)
Cellulitis † 1	1/92 (1.09%)
Localised infection † 1	1/92 (1.09%)
Pneumonia † 1	1/92 (1.09%)
Sepsis † 1	1/92 (1.09%)
Urosepsis † 1	1/92 (1.09%)
Injury, poisoning and procedural complications
Post procedural hematoma † 1	1/92 (1.09%)
Upper limb fracture † 1	1/92 (1.09%)
Investigations
Amylase increased † 1	1/92 (1.09%)
Lipase increased † 1	1/92 (1.09%)
Liver function test increased † 1	1/92 (1.09%)
Metabolism and nutrition disorders
Hyponatraemia † 1	2/92 (2.17%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia † 1	1/92 (1.09%)
Basal cell carcinoma † 1	5/92 (5.43%)
Keratoacanthoma † 1	1/92 (1.09%)
Malignant neoplasm of eyelid † 1	1/92 (1.09%)
Myelodysplastic syndrome † 1	1/92 (1.09%)
Squamous cell carcinoma † 1	6/92 (6.52%)
Squamous cell carcinoma of skin † 1	3/92 (3.26%)
Nervous system disorders
Aphasia † 1	1/92 (1.09%)
Epilepsy † 1	1/92 (1.09%)
Headache † 1	3/92 (3.26%)
Transient ischaemic attack † 1	1/92 (1.09%)
Psychiatric disorders
Confusional state † 1	2/92 (2.17%)
Mental status changes † 1	1/92 (1.09%)
Renal and urinary disorders
Acute kidney injury † 1	1/92 (1.09%)
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	1/92 (1.09%)
Pleural effusion † 1	1/92 (1.09%)
Pulmonary embolism † 1	1/92 (1.09%)
Social circumstances
Miscarriage of partner † 1	1/92 (1.09%)
Vascular disorders
Deep vein thrombosis † 1	1/92 (1.09%)
Haematoma † 1	2/92 (2.17%)
Hypertensive crisis † 1	1/92 (1.09%)
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	GSK2118436 150 mg
	Affected / at Risk (%)
Total	83/92 (90.22%)
Blood and lymphatic system disorders
Anaemia † 1	11/92 (11.96%)
Lymphopenia † 1	7/92 (7.61%)
Cardiac disorders
Tachycardia † 1	5/92 (5.43%)
Gastrointestinal disorders
Abdominal pain † 1	7/92 (7.61%)
Abdominal pain upper † 1	7/92 (7.61%)
Constipation † 1	7/92 (7.61%)
Diarrhoea † 1	11/92 (11.96%)
Nausea † 1	19/92 (20.65%)
Vomiting † 1	15/92 (16.30%)
General disorders
Asthenia † 1	8/92 (8.70%)
Chills † 1	13/92 (14.13%)
Fatigue † 1	22/92 (23.91%)
Oedema peripheral † 1	6/92 (6.52%)
Pyrexia † 1	24/92 (26.09%)
Infections and infestations
Bronchitis † 1	5/92 (5.43%)
Nasopharyngitis † 1	13/92 (14.13%)
Investigations
Blood alkaline phosphatase increased † 1	5/92 (5.43%)
Weight decreased † 1	6/92 (6.52%)
Metabolism and nutrition disorders
Decreased appetite † 1	14/92 (15.22%)
Hyperglycaemia † 1	5/92 (5.43%)
Hypophosphataemia † 1	9/92 (9.78%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	33/92 (35.87%)
Back pain † 1	9/92 (9.78%)
Musculoskeletal pain † 1	8/92 (8.70%)
Myalgia † 1	8/92 (8.70%)
Pain in extremity † 1	15/92 (16.30%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus † 1	10/92 (10.87%)
Seborrhoeic keratosis † 1	12/92 (13.04%)
Skin papilloma † 1	15/92 (16.30%)
Nervous system disorders
Headache † 1	19/92 (20.65%)
Psychiatric disorders
Anxiety † 1	5/92 (5.43%)
Depression † 1	5/92 (5.43%)
Insomnia † 1	5/92 (5.43%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	12/92 (13.04%)
Dyspnoea † 1	11/92 (11.96%)
Skin and subcutaneous tissue disorders
Actinic keratosis † 1	8/92 (8.70%)
Alopecia † 1	15/92 (16.30%)
Dry skin † 1	11/92 (11.96%)
Erythema † 1	8/92 (8.70%)
Hyperhidrosis † 1	6/92 (6.52%)
Hyperkeratosis † 1	27/92 (29.35%)
Palmoplantar keratoderma † 1	8/92 (8.70%)
Pruritus † 1	9/92 (9.78%)
Pruritus generalised † 1	5/92 (5.43%)
Rash † 1	10/92 (10.87%)
Transient acantholytic dermatosis † 1	6/92 (6.52%)
Vascular disorders
Hot flush † 1	6/92 (6.52%)
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

This study met the criteria for completed. Participants who were still receiving study treatment at the time the study was closed were given the option to transfer to a rollover protocol.

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.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343

Publications:

Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin AM, Mazumdar J, Goodman VL, Trefzer U. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 2013 Sep 10;31(26):3205-11. doi: 10.1200/JCO.2013.49.8691. Epub 2013 Aug 5.

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

Hauschild A, Ascierto PA, Schadendorf D, Grob JJ, Ribas A, Kiecker F, Dutriaux C, Demidov LV, Lebbe C, Rutkowski P, Blank CU, Gutzmer R, Millward M, Kefford R, Haas T, D'Amelio A Jr, Gasal E, Mookerjee B, Chapman PB. Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib monotherapy: Analysis from phase 2 and 3 clinical trials. Eur J Cancer. 2020 Jan;125:114-120. doi: 10.1016/j.ejca.2019.10.033.

Santiago-Walker A, Gagnon R, Mazumdar J, Casey M, Long GV, Schadendorf D, Flaherty K, Kefford R, Hauschild A, Hwu P, Haney P, O'Hagan A, Carver J, Goodman V, Legos J, Martin AM. Correlation of BRAF Mutation Status in Circulating-Free DNA and Tumor and Association with Clinical Outcome across Four BRAFi and MEKi Clinical Trials. Clin Cancer Res. 2016 Feb 1;22(3):567-74. doi: 10.1158/1078-0432.CCR-15-0321. Epub 2015 Oct 7.

Ouellet D, Gibiansky E, Leonowens C, O'Hagan A, Haney P, Switzky J, Goodman VL. Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites. J Clin Pharmacol. 2014 Jun;54(6):696-706. doi: 10.1002/jcph.263. Epub 2014 Jan 17.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01153763
• Other Study ID Numbers: 113710
• First Submitted: May 27, 2010
• First Posted: June 30, 2010
• Results First Submitted: June 12, 2013
• Results First Posted: June 2, 2014
• Last Update Posted: September 27, 2017