Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer

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ClinicalTrials.gov Identifier: NCT01902173

Recruitment Status : Active, not recruiting

First Posted : July 18, 2013

Results First Posted : October 14, 2020

Last Update Posted : December 6, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

GlaxoSmithKline

Novartis Pharmaceuticals

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Hematopoietic and Lymphoid Cell Neoplasm Locally Advanced Malignant Solid Neoplasm Locally Advanced Melanoma Metastatic Malignant Solid Neoplasm Metastatic Melanoma Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Unresectable Malignant Solid Neoplasm Unresectable Melanoma
Interventions	Procedure: Biopsy Procedure: Biospecimen Collection Procedure: Computed Tomography Drug: Dabrafenib Mesylate Procedure: Magnetic Resonance Imaging Drug: Trametinib Dimethyl Sulfoxide Drug: Uprosertib
Enrollment	27

Participant Flow

Recruitment Details
Pre-assignment Details	27 participants were enrolled, however 1 participant on the Dabrafenib + GSK2141795 75 mg arm and 1 participant on the Dabrafenib + Trametinib 1.5mg + GSK2141795 25mg were found to be ineligible. Furthermore, 3 participants on the Dabrafenib + GSK2141795 75 mg arm did not receive protocol treatment were not evaluable for any study endpoint.


Arm/Group Title	Dabrafenib + GSK2141795 50 mg	Dabrafenib + GSK2141795 75 mg	Dabrafenib + Trametinib 1.5mg + GSK2141795 25mg	Dabrafenib + Trametinib 1.5mg + GSK2141795 50mg	Dabrafenib + Trametinib 1.5mg + GSK2141795 75mg	Dabrafenib + Trametinib 2.0mg + GSK2141795 75mg
Arm/Group Description	Doublet regimen cohort 1: participa...	Doublet regimen cohort 2: participa...	Triplet regimen cohort 1: participa...	Triplet regimen cohort 2: participa...	Triplet regimen cohort 3: participa...	Triplet regimen cohort 4: participa...
Arm/Group Description	Doublet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily and 50 mg of GSK2141795 once daily.	Doublet regimen cohort 2: participants were given 150 mg of dabrafenib twice daily and 75 mg of GSK2141795 once daily.	Triplet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 25mg of GSK2141795 once daily.	Triplet regimen cohort 2: participants were given 150mg of dabrafenib twice daily, 1.5mg of trametinib and 50mg of GSK2141795 once daily.	Triplet regimen cohort 3: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 75mg of GSK2141795 once daily.	Triplet regimen cohort 4: participants were given 150 mg of dabrafenib twice daily, 2 mg of trametinib and 75 mg of GSK2141795 once daily.
Period Title: Phase 1 Doublet Regimen Cohort 1
Started	3	0	0	0	0	0
Completed	0	0	0	0	0	0
Not Completed	3	0	0	0	0	0
Reason Not Completed
Adverse Event	1	0	0	0	0	0
Progression/relapse	2	0	0	0	0	0
Period Title: Phase 1 Doublet Regimen Cohort 2
Started	0	9	0	0	0	0
Completed	0	0	0	0	0	0
Not Completed	0	9	0	0	0	0
Reason Not Completed
Progression/relapse	0	5	0	0	0	0
Ineligible	0	1	0	0	0	0
No treated	0	3	0	0	0	0
Period Title: Phase 1 Triplet Regimen Cohort 1
Started	0	0	4	0	0	0
Completed	0	0	0	0	0	0
Not Completed	0	0	4	0	0	0
Reason Not Completed
Progression/relapse	0	0	3	0	0	0
Ineligible	0	0	1	0	0	0
Period Title: Phase 1 Triplet Regimen Cohort 2
Started	0	0	0	3	0	0
Completed	0	0	0	0	0	0
Not Completed	0	0	0	3	0	0
Reason Not Completed
Ongoing treatment	0	0	0	1	0	0
Progression/relapse	0	0	0	2	0	0
Period Title: Phase 1 Triplet Regimen Cohort 3
Started	0	0	0	0	3	0
Completed	0	0	0	0	0	0
Not Completed	0	0	0	0	3	0
Reason Not Completed
Ongoing	0	0	0	0	1	0
Progression/relapse	0	0	0	0	2	0
Period Title: Phase 1 Triplet Regimen Cohort 4
Started	0	0	0	0	0	5
Completed	0	0	0	0	0	0
Not Completed	0	0	0	0	0	5
Reason Not Completed
Adverse Event	0	0	0	0	0	1
Progression/relapse	0	0	0	0	0	3
Death	0	0	0	0	0	1
Period Title: Phase II
Started	0	0	0	0	0	0
Completed	0	0	0	0	0	0
Not Completed	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title		Dabrafenib + GSK2141795 50 mg	Dabrafenib + GSK2141795 75 mg	Dabrafenib + Trametinib 1.5mg + GSK2141795 25mg	Dabrafenib + Trametinib 1.5mg + GSK2141795 50mg	Dabrafenib + Trametinib 1.5mg + GSK2141795 75mg	Dabrafenib + Trametinib 2.0mg + GSK2141795 75mg	Total
Arm/Group Description		Doublet regimen cohort 1: participa...	Doublet regimen cohort 2: participa...	Triplet regimen cohort 1: participa...	Triplet regimen cohort 2: participa...	Triplet regimen cohort 3: participa...	Triplet regimen cohort 4: participa...	Total of all reporting groups
Arm/Group Description		Doublet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily and 50 mg of GSK2141795 once daily.	Doublet regimen cohort 2: participants were given 150 mg of dabrafenib twice daily and 75 mg of GSK2141795 once daily	Triplet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 25mg of GSK2141795 once daily.	Triplet regimen cohort 2: participants were given 150mg of dabrafenib twice daily, 1.5mg of trametinib and 50mg of GSK2141795 once daily	Triplet regimen cohort 3: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 75mg of GSK2141795 once daily.	Triplet regimen cohort 4: participants were given 150 mg of dabrafenib twice daily, 2 mg of trametinib and 75 mg of GSK2141795 once daily.	Total of all reporting groups
Overall Number of Baseline Participants		3	5	3	3	3	5	22
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Total number of eligible and evaluable patients i.e. patients that received at least one dose of protocol therapy.
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	3 participants	5 participants	3 participants	3 participants	3 participants	5 participants	22 participants
		60.7 (52.0 to 65.8)	64.4 (40.5 to 70.2)	63.9 (45.7 to 68.5)	40.1 (18.5 to 57.5)	56.7 (28.5 to 70.2)	50.4 (48.8 to 77.1)	58.1 (18.5 to 77.1)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	3 participants	5 participants	3 participants	3 participants	3 participants	5 participants	22 participants
	Female	0 0.0%	1 20.0%	1 33.3%	2 66.7%	2 66.7%	2 40.0%	8 36.4%
	Male	3 100.0%	4 80.0%	2 66.7%	1 33.3%	1 33.3%	3 60.0%	14 63.6%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	3 participants	5 participants	3 participants	3 participants	3 participants	5 participants	22 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	3 100.0%	5 100.0%	3 100.0%	3 100.0%	2 66.7%	5 100.0%	21 95.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	1 4.5%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	3 participants	5 participants	3 participants	3 participants	3 participants	5 participants	22 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	3 100.0%	5 100.0%	3 100.0%	3 100.0%	2 66.7%	5 100.0%	21 95.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	1 4.5%
Prior BRAF inhibitor Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	3 participants	5 participants	3 participants	3 participants	3 participants	5 participants	22 participants
	Yes	2 66.7%	4 80.0%	1 33.3%	1 33.3%	2 66.7%	3 60.0%	13 59.1%
	No	1 33.3%	1 20.0%	2 66.7%	2 66.7%	1 33.3%	1 20.0%	8 36.4%
	Not reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 20.0%	1 4.5%
Type of cancer Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	3 participants	5 participants	3 participants	3 participants	3 participants	5 participants	22 participants
	Melanoma	2 66.7%	4 80.0%	2 66.7%	3 100.0%	3 100.0%	4 80.0%	18 81.8%
	Lung	0 0.0%	1 20.0%	1 33.3%	0 0.0%	0 0.0%	1 20.0%	3 13.6%
	Thyroid	1 33.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 4.5%

Outcome Measures

1.Primary Outcome


Title	Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib.
Description	MTD was evaluated by testing increasing doses up to 75 mg once a day, ...
Description	MTD was evaluated by testing increasing doses up to 75 mg once a day, given in combination with dabrafenib dosed at 150 mg twice daily. MTD reflects the highest dose that did not cause a DLT. DLTs were defined as treatment regimen related: febrile neutropenia; Grade 4 neutropenia lasting more than 7 days; Grade 4 platelet count decrease; Grade 3-4 rash, fever, or hyperglycemia > 14 days, e) Grade 3-4 non-hematologic adverse events lasting greater than 7 days. Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame	Every 2 weeks during days 1-56 of treatment.

Outcome Measure Data

Analysis Population Description

Eligible, analyzable and evaluable participants that were assessed for DLT. In the Dabrafenib + GSK2141795 75 mg arm, 1 participant was ineligible, 3 participants were not analyzable, and 1 participant did not satisfy protocol-specified criteria for DLT evaluation. These patients were excluded from DLT analysis.


Arm/Group Title	Phase 1 Doublet Regimen
Arm/Group Description:	All analyzable patients who experie...
Arm/Group Description:	All analyzable patients who experienced a dose limiting toxicity OR at least received GSK2141795 for 11 days in Cycle 1 and dabrafenib for 28 days in cycles 1 and 2 OR at least received GSK2141795 for 11 days in Cycle 1 and 50% of dabrafenib in Cycle 1
Overall Number of Participants Analyzed	7
Measure Type: Number Unit of Measure: mg
	75

2.Primary Outcome


Title	Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib and Trametinib.
Description	MTD was evaluated by testing increasing doses up to 75 mg once a day, ...
Description	MTD was evaluated by testing increasing doses up to 75 mg once a day, given in combination with dabrafenib dosed at 150 mg twice daily and trametinib at either 1.5 mg or 2 mg once a day. MTD reflects the highest dose that did not cause a dose-limiting toxicity (DLT). DLTs were defined as treatment regimen related: febrile neutropenia; Grade 4 neutropenia lasting more than 7 days; Grade 4 platelet count decrease; Grade 3-4 rash, fever, or hyperglycemia > 14 days, e) Grade 3-4 non-hematologic adverse events lasting greater than 7 days. Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Note: MTD for the triplet regimen could not be determined due to the end of supply of the study drug. Number reported is the maximum dose of GSK2141795 that was assessed in combination with 150 mg Dabrafenib and 2 mg trametinib.
Time Frame	Every 2 weeks during days 1-56 of treatment.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants that were assessed for DLT. 1 participant in the Dabrafenib + Trametinib 1.5 mg + GSK2141795 25 mg was not eligible. 1 participant in the Dabrafenib + Trametinib 2.0 mg + GSK2141795 75 mg arm did not satisfy protocol-specified criteria for DLT evaluation and was thus excluded.


Arm/Group Title	Phase 1 Triplet Regimen
Arm/Group Description:	All analyzable patients who experie...
Arm/Group Description:	All analyzable patients who experienced a dose limiting toxicity OR at least received GSK2141795 for 11 days in Cycle 1 and dabrafenib and trametinib for 28 days each in cycles 1 and 2 OR at least received GSK2141795 for 11 days in Cycle1 and 50% of dabrafenib and trametinib each in Cycle 1
Overall Number of Participants Analyzed	13
Measure Type: Number Unit of Measure: mg
	75

3.Primary Outcome


Title	Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses) as Assessed by RECIST Version 1.1 of the Doublet Regimen GSK2141795 + Dabrafenib at the Phase I Determined MTD. (Phase II)
Description	All measurable lesions up to a maximum of 2 lesions per organ 5 lesion...
Description	All measurable lesions up to a maximum of 2 lesions per organ 5 lesions in total, representative of all involved organs, were identified as target lesions at baseline. All other lesions (or sites of disease) were identified as non-target lesions. Complete Response (CR): Complete disappearance of all target and nontarget lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to < 1.0 cm. Partial Response (PR): <= 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Unconfirmed CR: One objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR: One objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Time Frame	Disease assessments every 8 weeks for up to 3 years

Outcome Measure Data

Analysis Population Description

No participants were enrolled to Phase II portion due to the end of the supply of GSK2141795


Arm/Group Title	Dabrafenib + GSK2141795 at MTD
Arm/Group Description:	Patients who received at least one ...
Arm/Group Description:	Patients who received at least one dose of protocol therapy at the Phase I determined MTD.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

4.Primary Outcome


Title	Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses) as Assessed by RECIST Version 1.1 of the Triplet Regimen GSK2141795 + Dabrafenib + Trametinib at the Phase I Determined MTD. (Phase II)
Description	All measurable lesions up to a maximum of 2 lesions per organ 5 lesion...
Description	All measurable lesions up to a maximum of 2 lesions per organ 5 lesions in total, representative of all involved organs, were identified as target lesions at baseline. All other lesions (or sites of disease) were identified as non-target lesions. Complete Response (CR): Complete disappearance of all target and nontarget lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to < 1.0 cm. Partial Response (PR): <= 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Unconfirmed CR: One objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR: One objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Time Frame	Disease assessments every 8 weeks for up to 3 years

Outcome Measure Data

Analysis Population Description

No participants were enrolled to Phase II portion due to the end of the supply of GSK2141795


Arm/Group Title	Dabrafenib + Trametinib + GSK2141795 at MTD
Arm/Group Description:	Patients who received at least one ...
Arm/Group Description:	Patients who received at least one dose of protocol therapy at the Phase I determined MTD.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

5.Secondary Outcome


Title	Overall Survival (Phase II) of Patients Treated at the Phase I Determined MTD of Doublet Regimen
Description	Estimated with 95% confidence interval.
Description	Estimated with 95% confidence interval.
Time Frame	From date of registration to date of death due to any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

No participants were enrolled to Phase II portion due to the end of the supply of GSK2141795


Arm/Group Title	GSK2141795 + Dabrafenib at the Phase I Determined MTD
Arm/Group Description:	Patients who received at least 1 do...
Arm/Group Description:	Patients who received at least 1 dose of protocol therapy at the Phase I determined MTD
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

6.Secondary Outcome


Title	Overall Survival (Phase II) of Patients Treated at the Phase I Determined MTD of Triplet Regimen
Description	Estimated with 95% confidence interval.
Description	Estimated with 95% confidence interval.
Time Frame	From date of registration to date of death due to any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

No participants were enrolled to Phase II portion due to the end of the supply of GSK2141795


Arm/Group Title	GSK2141795 + Dabrafenib + Trametinib at Phase I Determined MTD
Arm/Group Description:	Patients who received at least 1 do...
Arm/Group Description:	Patients who received at least 1 dose of protocol therapy at the Phase I determined MTD
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

7.Secondary Outcome


Title	Progression-free Survival as Assessed by RECIST Version 1.1 of the Doublet Regimen at the Phase I Determined MTD (Phase II)
Description	Estimated with 95% confidence interval.
Description	Estimated with 95% confidence interval.
Time Frame	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

No participants were enrolled to Phase II portion due to the end of the supply of GSK2141795


Arm/Group Title	Dabrafenib + GSK2141795 at Phase I Determined MTD
Arm/Group Description:	Patients who received at least one ...
Arm/Group Description:	Patients who received at least one dose of protocol therapy at the Phase I determined MTD.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

8.Secondary Outcome


Title	Progression-free Survival as Assessed by RECIST Version 1.1 of the Triplet Regimen at the Phase I Determined MTD (Phase II)
Description	Estimated with 95% confidence interval.
Description	Estimated with 95% confidence interval.
Time Frame	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

No participants were enrolled to Phase II portion due to the end of the supply of GSK2141795


Arm/Group Title	Dabrafenib + Trametinib + GSK2141795 at Phase I Determined MTD
Arm/Group Description:	Patients who received at least one ...
Arm/Group Description:	Patients who received at least one dose of protocol therapy at the phase I determined MTD
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

9.Secondary Outcome


Title	Toxicity Rate of MTD Graded by the NCI CTCAE Version 4.0 (Phase II)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

No participants were enrolled to the Phase II portion due to the end of the supply of GSK2141795


Arm/Group Title	Dabrafenib + GSK2141795 75 mg
Arm/Group Description:	All participants on the Phase II tr...
Arm/Group Description:	All participants on the Phase II triplet combination of dabrafenib, trametinib and GSK2141795 MTD .
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

10.Other Pre-specified Outcome


Title	Pharmacokinetic Parameters
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, pre-dose and 1, 2, 4, and 8 hours on day 15, and pre-dose day 29

Outcome Measure Data Not Reported

11.Other Pre-specified Outcome


Title	Prevalence of Markers
Description	For binary markers, the prevalence will be able to be estimated and ex...
Description	For binary markers, the prevalence will be able to be estimated and exact binomial confidence interval will be calculated. The association between these categorical markers and clinical outcomes will be explored in a preliminary manner, using Fisher's exact test to compare response and a logrank test to compare Kaplan-Meier estimates of overall survival and progression free survival between marker positive and marker negative groups.
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

Adverse Events

Time Frame	3 years
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Dabrafenib + GSK2141795 50 mg	Dabrafenib + GSK2141795 75 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 25 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 50 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 75 mg	Dabrafenib + Trametinib 2 mg + GSK2141795 75 mg
Arm/Group Description	Doublet regimen cohort 1: participa...	Doublet regimen cohort 2: participa...	Triplet regimen cohort 1: participa...	Triplet regimen cohort 2: participa...	Triplet regimen cohort 3: participa...	Triplet regimen cohort 4: participa...
Arm/Group Description	Doublet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily and 50 mg of GK2141795 once daily.	Doublet regimen cohort 2: participants were given 150 mg of dabrafenib twice daily and 75 mg of GK2141795 once daily.	Triplet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 25 mg of GK2141795 once daily.	Triplet regimen cohort 2: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 50 mg of GK2141795 once daily.	Triplet regimen cohort 3: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 75 mg of GK2141795 once daily.	Triplet regimen cohort 4: participants were given 150 mg of dabrafenib twice daily, 2 mg of trametinib and 75 mg of GK2141795 once daily.
All-Cause Mortality
	Dabrafenib + GSK2141795 50 mg	Dabrafenib + GSK2141795 75 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 25 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 50 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 75 mg	Dabrafenib + Trametinib 2 mg + GSK2141795 75 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/3 (100.00%)	3/5 (60.00%)	2/3 (66.67%)	2/3 (66.67%)	2/3 (66.67%)	4/5 (80.00%)
Serious Adverse Events Serious Adverse Events
	Dabrafenib + GSK2141795 50 mg	Dabrafenib + GSK2141795 75 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 25 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 50 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 75 mg	Dabrafenib + Trametinib 2 mg + GSK2141795 75 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/3 (66.67%)	2/5 (40.00%)	2/3 (66.67%)	1/3 (33.33%)	1/3 (33.33%)	5/5 (100.00%)
Cardiac disorders
Atrial fibrillation ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Gastrointestinal disorders
Abdominal pain ^†	0/3 (0.00%)	2/5 (40.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Nausea ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Small intestinal obstruction ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Upper gastrointestinal hemorrhage ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
General disorders
Fatigue ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Fever ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/5 (60.00%)
General disorders and admin site conditions - Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Localized edema ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Non-cardiac chest pain ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Immune system disorders
Allergic reaction ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Infections and infestations
Lung infection ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Sepsis ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Urinary tract infection ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Metabolism and nutrition disorders
Dehydration ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Hypercalcemia ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Hyperglycemia ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Hypokalemia ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Hyponatremia ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Hypophosphatemia ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Musculoskeletal and connective tissue disorders
Flank pain ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Pain in extremity ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other ^†	1/3 (33.33%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	2/5 (40.00%)
Tumor pain ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Nervous system disorders
Seizure ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/5 (0.00%)
Syncope ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Psychiatric disorders
Confusion ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Skin and subcutaneous tissue disorders
Rash maculo-papular ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Skin and subcutaneous tissue disorders - Other ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Vascular disorders
Thromboembolic event ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Dabrafenib + GSK2141795 50 mg	Dabrafenib + GSK2141795 75 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 25 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 50 mg	Dabrafenib + Trametinib 1.5 mg + GSK2141795 75 mg	Dabrafenib + Trametinib 2 mg + GSK2141795 75 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/3 (100.00%)	5/5 (100.00%)	3/3 (100.00%)	3/3 (100.00%)	3/3 (100.00%)	5/5 (100.00%)
Blood and lymphatic system disorders
Anemia ^†	1/3 (33.33%)	3/5 (60.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Febrile neutropenia ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Cardiac disorders
Cardiac disorders-Other ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Sinus tachycardia ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders - Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Ear and labyrinth disorders
Ear pain ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Tinnitus ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Eye disorders
Dry eye ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Eye disorders-Other ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Flashing lights ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Uveitis ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Gastrointestinal disorders
Abdominal pain ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	0/5 (0.00%)
Ascites ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Constipation ^†	1/3 (33.33%)	0/5 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	0/3 (0.00%)	3/5 (60.00%)
Diarrhea ^†	1/3 (33.33%)	2/5 (40.00%)	1/3 (33.33%)	0/3 (0.00%)	2/3 (66.67%)	2/5 (40.00%)
Dyspepsia ^†	0/3 (0.00%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Gastroesophageal reflux disease ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Gastrointestinal disorders-Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Mucositis oral ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Nausea ^†	2/3 (66.67%)	3/5 (60.00%)	1/3 (33.33%)	1/3 (33.33%)	3/3 (100.00%)	3/5 (60.00%)
Vomiting ^†	2/3 (66.67%)	2/5 (40.00%)	2/3 (66.67%)	2/3 (66.67%)	1/3 (33.33%)	2/5 (40.00%)
General disorders
Chills ^†	1/3 (33.33%)	2/5 (40.00%)	2/3 (66.67%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Edema limbs ^†	2/3 (66.67%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Fatigue ^†	3/3 (100.00%)	3/5 (60.00%)	3/3 (100.00%)	1/3 (33.33%)	1/3 (33.33%)	3/5 (60.00%)
Fever ^†	1/3 (33.33%)	1/5 (20.00%)	2/3 (66.67%)	2/3 (66.67%)	1/3 (33.33%)	2/5 (40.00%)
Flu like symptoms ^†	1/3 (33.33%)	2/5 (40.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Gait disturbance ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
General disorders and admin site conditions - Other ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Irritability ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Malaise ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Non-cardiac chest pain ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Pain ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Hepatobiliary disorders
Gallbladder obstruction ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Immune system disorders
Allergic reaction ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Infections and infestations
Bronchial infection ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Infections and infestations-Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Lung infection ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Otitis media ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Papulopustular rash ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Pharyngitis ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Sepsis ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Sinusitis ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/5 (0.00%)
Soft tissue infection ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/5 (0.00%)
Upper respiratory infection ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/5 (20.00%)
Urinary tract infection ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Injury, poisoning and procedural complications
Bruising ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Fall ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Injury, poison and procedural complications - Other ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Investigations
Activated partial thromboplastin time prolonged ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Alanine aminotransferase increased ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/3 (33.33%)	1/5 (20.00%)
Alkaline phosphatase increased ^†	1/3 (33.33%)	0/5 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/3 (33.33%)	0/5 (0.00%)
Aspartate aminotransferase increased ^†	1/3 (33.33%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Creatinine increased ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
INR increased ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Investigations-Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	0/5 (0.00%)
Lipase increased ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Lymphocyte count decreased ^†	2/3 (66.67%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Neutrophil count decreased ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	3/5 (60.00%)
Platelet count decreased ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Weight loss ^†	2/3 (66.67%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
White blood cell decreased ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	3/5 (60.00%)
Metabolism and nutrition disorders
Anorexia ^†	2/3 (66.67%)	3/5 (60.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Dehydration ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	2/5 (40.00%)
Hypercalcemia ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Hyperglycemia ^†	2/3 (66.67%)	2/5 (40.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Hypernatremia ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Hypoalbuminemia ^†	1/3 (33.33%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Hypocalcemia ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Hypokalemia ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Hypomagnesemia ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Hyponatremia ^†	1/3 (33.33%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Hypophosphatemia ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Back pain ^†	0/3 (0.00%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Bone pain ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Chest wall pain ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/5 (0.00%)
Flank pain ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Generalized muscle weakness ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	2/5 (40.00%)
Joint effusion ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/5 (0.00%)
Muscle weakness upper limb ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Musculoskeletal and connective tiss disorder - Other ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Myalgia ^†	2/3 (66.67%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Neck pain ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/5 (20.00%)
Pain in extremity ^†	2/3 (66.67%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	2/5 (40.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Tumor pain ^†	0/3 (0.00%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Nervous system disorders
Dizziness ^†	1/3 (33.33%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Dysphasia ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Headache ^†	0/3 (0.00%)	2/5 (40.00%)	0/3 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	3/5 (60.00%)
Nervous system disorders-Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Peripheral sensory neuropathy ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Presyncope ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Sinus pain ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	0/5 (0.00%)
Somnolence ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Tremor ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Vasovagal reaction ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Psychiatric disorders
Anxiety ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/5 (20.00%)
Confusion ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Depression ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Insomnia ^†	1/3 (33.33%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Psychiatric disorders-Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Renal and urinary disorders
Hematuria ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Proteinuria ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Renal and urinary disorders-Other ^†	0/3 (0.00%)	2/5 (40.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Urinary frequency ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Urinary incontinence ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Reproductive system and breast disorders
Vaginal inflammation ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/5 (0.00%)
Cough ^†	1/3 (33.33%)	2/5 (40.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Dyspnea ^†	2/3 (66.67%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Epistaxis ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Hypoxia ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Nasal congestion ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/5 (20.00%)
Pleuritic pain ^†	2/3 (66.67%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Pneumonitis ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Postnasal drip ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Productive cough ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Resp, thoracic and mediastinal disorders - Other ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Sore throat ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia ^†	0/3 (0.00%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Bullous dermatitis ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Dry skin ^†	0/3 (0.00%)	1/5 (20.00%)	2/3 (66.67%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Erythema multiforme ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Hyperhidrosis ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Nail discoloration ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Nail ridging ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Pain of skin ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Palmar-plantar erythrodysesthesia syndrome ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Photosensitivity ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Pruritus ^†	1/3 (33.33%)	1/5 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	0/5 (0.00%)
Rash acneiform ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Rash maculo-papular ^†	1/3 (33.33%)	2/5 (40.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	3/5 (60.00%)
Scalp pain ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Skin and subcutaneous tissue disorders - Other ^†	1/3 (33.33%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Skin hypopigmentation ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Telangiectasia ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Urticaria ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Vascular disorders
Capillary leak syndrome ^†	0/3 (0.00%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/5 (40.00%)
Flushing ^†	0/3 (0.00%)	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Hypertension ^†	0/3 (0.00%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/5 (20.00%)
Hypotension ^†	1/3 (33.33%)	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	1/5 (20.00%)
Thromboembolic event ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
Vascular disorders-Other ^†	1/3 (33.33%)	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/5 (0.00%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

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Name/Title:	Melanoma Statistician
Organization:	SWOG
Phone:	2066674623
EMail:	jmoon@fredhutch.org

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01902173
Other Study ID Numbers:	NCI-2013-01320 NCI-2013-01320 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) SWOG-S1221 S1221 ( Other Identifier: SWOG ) S1221 ( Other Identifier: CTEP ) U10CA180830 ( U.S. NIH Grant/Contract ) U10CA180888 ( U.S. NIH Grant/Contract ) U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted:	July 15, 2013
First Posted:	July 18, 2013
Results First Submitted:	May 13, 2019
Results First Posted:	October 14, 2020
Last Update Posted:	December 6, 2022

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