Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of GSK1120212 Plus Gemcitabine vs Placebo Plus Gemcitabine in Metastatic Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01231581
Recruitment Status : Completed
First Posted : November 1, 2010
Results First Posted : September 26, 2013
Last Update Posted : September 26, 2013
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cancer
Interventions Drug: GSK1120212
Drug: Gemcitabine
Drug: Placebo
Enrollment 160
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason. Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Period Title: Overall Study
Started 80 80
Ongoing 1 [1] 0
Completed 0 0
Not Completed 80 80
Reason Not Completed
Lost to Follow-up             2             2
Withdrawal by Subject             6             9
Study Closed/Terminated             6             5
Death             65             64
Ongoing             1             0
[1]
Participant is continuing treatment with trametinib and gemcitabine under roll over study MEK114375.
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine Total
Hide Arm/Group Description Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason. Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason. Total of all reporting groups
Overall Number of Baseline Participants 80 80 160
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 80 participants 80 participants 160 participants
62.3  (10.35) 62.2  (9.56) 62.3  (9.93)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 80 participants 160 participants
Female
41
  51.2%
34
  42.5%
75
  46.9%
Male
39
  48.8%
46
  57.5%
85
  53.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 80 participants 80 participants 160 participants
White - White/Caucasian/European Heritage 50 59 109
Asian - East Asian Heritage 24 13 37
African American Africa 6 5 11
Asian - Central/South Asian Heritage 0 1 1
Asian - South East Asian Heritage 0 1 1
White - Arabic/North African Heritage 0 1 1
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the time from randomization until death due to any cause. For the analysis of overall survival, the last date of known contact was used for those participants who were not dead at the time of analysis; such participants were considered censored.
Time Frame From randomization until death due to any cause or until the data cutoff of 15-March-2013 (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not treatment was administered
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description:
Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Overall Number of Participants Analyzed 80 80
Median (95% Confidence Interval)
Unit of Measure: months
8.4
(7.8 to 10.3)
6.7
(5.3 to 9.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trametinib + Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.352
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.66 to 1.32
Estimation Comments Hazard ratios are estimated using a Pike estimator.
2.Secondary Outcome
Title Progression-free Survival (PFS) as Assessed by the Investigator
Hide Description PFS is defined as the time from randomization until the earliest date of radiological PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). PD was also based on unequivocal progression of existing non-target lesions. If the participant received subsequent anti-cancer therapy prior to the date of documented progression or death, or did not have a documented date of progression or death, PFS was censored at the last adequate assessment.
Time Frame From randomization until disease progression (PD) or death due to any cause or until the data cutoff of 17-April-2012 (up to 15 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description:
Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Overall Number of Participants Analyzed 80 80
Median (95% Confidence Interval)
Unit of Measure: weeks
16.1
(14.0 to 23.4)
15.1
(8.6 to 21.7)
3.Secondary Outcome
Title Number of Participants With an Investigator-assessed Best Response, With or Without Confirmation, of Complete Response (CR) or Partial Response (PR)
Hide Description CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR is defined as at least a 30% 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). CR and PR were evaluated by the Investigator using standard criteria (RECIST version 1.1). Confirmation of response was not required.
Time Frame From randomization until disease progression or death due to any cause or until the data cutoff of 17-April-2012 (up to 15 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Measurable Disease (MD) Population: all randomized participants regardless of whether or not treatment was administered who had measurable disease at baseline
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description:
Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Overall Number of Participants Analyzed 77 77
Measure Type: Number
Unit of Measure: participants
CR 1 0
PR 16 14
4.Secondary Outcome
Title Investigator-Assessed Duration of Response
Hide Description Duration of response is defined, for the subset of participants with a CR or PR, as the time from the first documented evidence of CR or PR until the first documented disease progression or death due to any cause. CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR is defined as at least a 30% 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). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start).
Time Frame From the first documented CR or PR until disease progression or death due to any cause or until the data cutoff of 17-April-2012 (up to 13 months)
Hide Outcome Measure Data
Hide Analysis Population Description
MD Population. Duration of response was assessed for only those participants with a CR or PR.
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description:
Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Overall Number of Participants Analyzed 17 14
Median (95% Confidence Interval)
Unit of Measure: Weeks
23.9
(9.0 to 28.9)
16.1 [1] 
(8.3 to NA)
[1]
There were too few events to provide an estimable upper limit of the confidence interval.
5.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Per protocol other events were considered SAEs like symptomatic left ventricular ejection fraction (LVEF) decreases or cases of central serous retinopathy (CSR) or retinal vein occlusion (RVO). AE and SAE data were collected from the start of the first dose of study treatment and continued until 28 days following discontinuation of the study treatment or death. Refer to the general AE/SAE module for a complete list of AEs and SAEs.
Time Frame From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 15-March-2013 (up to 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description:
Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Overall Number of Participants Analyzed 80 80
Measure Type: Number
Unit of Measure: participants
Any AE 80 80
SAE 42 37
6.Secondary Outcome
Title Number of Participants (Par.) With a Worst-case Change to Grade 3 or Grade 4 From Baseline Grade in Chemistry Parameters
Hide Description A grading (severity) scale is provided for each laboratory toxicity. Grade refers to the severity of the toxicity. The Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 displays Grades 1 through 5 based on the general guideline: Grade 1, mild toxicity; Grade 2, moderate toxicity; Grade 3, severe toxicity; Grade 4, life-threatening or disabling toxicity; Grade 5, death related to toxicity.
Time Frame From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 17-April-2012 (up to 17 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. with laboratory values for worst-case on therapy were analyzed. The same par. were not necessarily analyzed for each laboratory parameter; thus, the number of par. analyzed reflects all par. in the Safety Population. The number of par. analyzed for a particular parameter is included in the parameter title.
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description:
Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Overall Number of Participants Analyzed 80 80
Measure Type: Number
Unit of Measure: participants
Albumin, Grade 3, n=73, 73 7 4
Albumin, Grade 4, n=73, 73 0 0
Alkaline Phosphatase, Grade 3, n=74, 73 7 4
Alkaline Phosphatase, Grade 4, n=74, 73 0 0
Alanine Amino Transferase, Grade 3, n=74, 73 7 7
Alanine Amino Transferase, Grade 4, n=74, 73 0 0
Aspartate Aminotransferase, Grade 3, n=73, 72 6 7
Aspartate Aminotransferase, Grade 4, n=73, 72 0 0
Total Bilirubin, Grade 3, n=74, 73 1 7
Total Bilirubin, Grade 4, n=74, 73 0 1
Calcium (hypercalcemia), Grade 3, n=73, 73 1 1
Calcium (hypercalcemia), Grade 4, n=73, 73 0 0
Calcium (hypocalcemia), Grade 3, n=73, 73 1 2
Calcium (hypocalcemia), Grade 4, n=73, 73 0 0
Creatinine, Grade 3, n=74, 75 0 0
Creatinine, Grade 4, n=74, 75 1 0
Glucose (hyperglycemia), Grade 3, n=74, 72 9 10
Glucose (hyperglycemia), Grade 4, n=74, 72 0 1
Glucose (hypoglycemia), Grade 3, n=74, 72 0 0
Glucose (hypoglycemia), Grade 4, n=74, 72 1 0
Potassium (hyperkalemia), Grade 3, n=74, 72 2 1
Potassium (hyperkalemia), Grade 4, n=74, 72 0 0
Potassium (hypokalemia), Grade 3, n=74, 72 4 1
Potassium (hypokalemia), Grade 4, n=74, 72 0 0
Sodium (hyponatremia), Grade 3, n=74, 74 5 3
Sodium (hyponatremia), Grade 4, n=74, 74 2 0
7.Secondary Outcome
Title Number of Participants With Change From Baseline Increase to Grade 3/Grade 4 in Lab Hematology Test Measurements
Hide Description A grading (severity) scale is provided for each laboratory toxicity. Grade refers to the severity of the toxicity. The CTCAE version 3.0 displays Grades 1 through 5, with unique clinical descriptions of the severity for each toxicity based on the general guideline: Grade 1, mild toxicity; Grade 2, moderate toxicity; Grade 3, severe toxicity; Grade 4, life-threatening or disabling toxicity; Grade 5, death related to toxicity.
Time Frame From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 17-April-2012 (up to 17 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. with laboratory values for worst-case on therapy were analyzed. The same par. were not necessarily analyzed for each laboratory parameter; thus, the number of par. analyzed reflects all par. in the Safety Population. The number of par. analyzed for a particular parameter is included in the parameter title.
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description:
Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
Overall Number of Participants Analyzed 80 80
Measure Type: Number
Unit of Measure: participants
Hemoglobin (Increased), Grade 3, n=80, 79 3 0
Hemoglobin (Increased), Grade 4, n=80, 79 0 0
Hemoglobin (Anemia), Grade 3, n=80, 79 24 13
Hemoglobin (Anemia), Grade 4, n=80, 79 0 0
Lymphocytes (Increased), Grade 3, n=80, 79 1 0
Lymphocytes (Increased), Grade 4, n=80, 79 0 0
Lymphocytes (Decreased), Grade 3, n=80, 79 9 12
Lymphocytes (Decreased), Grade 4, n=80, 79 3 6
Absolute Neutrophil Count, Grade 3, n=80, 79 23 20
Absolute Neutrophil Count, Grade 4, n=80, 79 7 10
Platelet count, Grade 3, n=80, 79 11 10
Platelet count, Grade 4, n=80, 79 1 4
White Blood Cell count, Grade 3, n=80, 79 15 14
White Blood Cell count, Grade 4, n=80, 79 1 4
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the time the first dose of study treatment was administered until 28 days following discontinuation of study treatment or until the data cutoff of 15-March-2013 (up to 21 months).
Adverse Event Reporting Description SAEs and non-serious AEs were collected in the Safety Population, comprised of all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.
 
Arm/Group Title Trametinib + Gemcitabine Placebo + Gemcitabine
Hide Arm/Group Description Participants received 2 milligrams (mg) trametinib orally once daily in combination with 1000 mg/m^2 of gemcitabine given as intravenous (IV) infusion over 30 minutes (min). In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or permanent discontinuation from study treatment for any reason. Participants received placebo orally once daily in combination with 1000 mg/m^2 of gemcitabine given as IV infusion over 30 min. In the first cycle, gemcitabine was infused weekly for 7 weeks followed by a week of rest from treatment and then subsequent cycles on Day 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment cycle until PD, unacceptable toxicity, or permanent discontinuation from study treatment for any reason.
All-Cause Mortality
Trametinib + Gemcitabine Placebo + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Trametinib + Gemcitabine Placebo + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   42/80 (52.50%)   37/80 (46.25%) 
Blood and lymphatic system disorders     
Anaemia  1  3/80 (3.75%)  2/80 (2.50%) 
Febrile neutropenia  1  1/80 (1.25%)  1/80 (1.25%) 
Pancytopenia  1  1/80 (1.25%)  1/80 (1.25%) 
Thrombocytopenia  1  1/80 (1.25%)  1/80 (1.25%) 
Leukopenia  1  1/80 (1.25%)  0/80 (0.00%) 
Cardiac disorders     
Tachycardia  1  0/80 (0.00%)  2/80 (2.50%) 
Angina pectoris  1  0/80 (0.00%)  1/80 (1.25%) 
Atrial fibrillation  1  0/80 (0.00%)  1/80 (1.25%) 
Cardiac failure congestive  1  0/80 (0.00%)  1/80 (1.25%) 
Ear and labyrinth disorders     
Ear pain  1  1/80 (1.25%)  0/80 (0.00%) 
Tympanic membrane perforation  1  1/80 (1.25%)  0/80 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  4/80 (5.00%)  1/80 (1.25%) 
Vomiting  1  3/80 (3.75%)  2/80 (2.50%) 
Nausea  1  3/80 (3.75%)  1/80 (1.25%) 
Intestinal obstruction  1  2/80 (2.50%)  1/80 (1.25%) 
Constipation  1  2/80 (2.50%)  0/80 (0.00%) 
Diarrhoea  1  2/80 (2.50%)  0/80 (0.00%) 
Aphthous stomatitis  1  1/80 (1.25%)  0/80 (0.00%) 
Enteritis  1  1/80 (1.25%)  0/80 (0.00%) 
Ileus  1  1/80 (1.25%)  0/80 (0.00%) 
Melaena  1  1/80 (1.25%)  0/80 (0.00%) 
Subileus  1  1/80 (1.25%)  1/80 (1.25%) 
Obstruction gastric  1  1/80 (1.25%)  2/80 (2.50%) 
Duodenal ulcer haemorrhage  1  1/80 (1.25%)  0/80 (0.00%) 
Abdominal pain lower  1  0/80 (0.00%)  1/80 (1.25%) 
Abdominal pain upper  1  0/80 (0.00%)  1/80 (1.25%) 
Gastrointestinal haemorrhage  1  0/80 (0.00%)  1/80 (1.25%) 
Oesophageal ulcer  1  0/80 (0.00%)  1/80 (1.25%) 
Oesophagitis  1  0/80 (0.00%)  1/80 (1.25%) 
Small intestinal obstruction  1  0/80 (0.00%)  1/80 (1.25%) 
General disorders     
Pyrexia  1  8/80 (10.00%)  2/80 (2.50%) 
Asthenia  1  1/80 (1.25%)  1/80 (1.25%) 
Device occlusion  1  1/80 (1.25%)  0/80 (0.00%) 
Mucosal inflammation  1  1/80 (1.25%)  0/80 (0.00%) 
Stent malfunction  1  1/80 (1.25%)  0/80 (0.00%) 
Fatigue  1  0/80 (0.00%)  2/80 (2.50%) 
Hepatobiliary disorders     
Cholangitis  1  1/80 (1.25%)  2/80 (2.50%) 
Bile duct obstruction  1  1/80 (1.25%)  0/80 (0.00%) 
Cholestasis  1  0/80 (0.00%)  2/80 (2.50%) 
Jaundice  1  0/80 (0.00%)  1/80 (1.25%) 
Jaundice cholestatic  1  0/80 (0.00%)  1/80 (1.25%) 
Infections and infestations     
Pneumonia  1  5/80 (6.25%)  2/80 (2.50%) 
Sepsis  1  3/80 (3.75%)  2/80 (2.50%) 
Biliary tract infection  1  2/80 (2.50%)  0/80 (0.00%) 
Bronchitis  1  1/80 (1.25%)  1/80 (1.25%) 
Urinary tract infection  1  1/80 (1.25%)  1/80 (1.25%) 
Device related infection  1  1/80 (1.25%)  0/80 (0.00%) 
Enterococcal bacteraemia  1  1/80 (1.25%)  0/80 (0.00%) 
Epstein-Barr virus infection  1  1/80 (1.25%)  0/80 (0.00%) 
Fungal infection  1  1/80 (1.25%)  0/80 (0.00%) 
Lung infection  1  1/80 (1.25%)  0/80 (0.00%) 
Otitis media  1  1/80 (1.25%)  0/80 (0.00%) 
Parotitis  1  1/80 (1.25%)  0/80 (0.00%) 
Tonsillitis  1  1/80 (1.25%)  0/80 (0.00%) 
Cellulitis  1  0/80 (0.00%)  3/80 (3.75%) 
Abdominal sepsis  1  0/80 (0.00%)  1/80 (1.25%) 
Clostridium difficile colitis  1  0/80 (0.00%)  1/80 (1.25%) 
Diverticulitis  1  0/80 (0.00%)  1/80 (1.25%) 
Liver abscess  1  0/80 (0.00%)  1/80 (1.25%) 
Postoperative abscess  1  0/80 (0.00%)  1/80 (1.25%) 
Respiratory tract infection  1  0/80 (0.00%)  1/80 (1.25%) 
Sinusitis  1  0/80 (0.00%)  1/80 (1.25%) 
Injury, poisoning and procedural complications     
Wound dehiscence  1  1/80 (1.25%)  0/80 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  4/80 (5.00%)  0/80 (0.00%) 
Aspartate aminotransferase increased  1  1/80 (1.25%)  0/80 (0.00%) 
Blood bilirubin increased  1  1/80 (1.25%)  0/80 (0.00%) 
Hepatic enzyme increased  1  1/80 (1.25%)  0/80 (0.00%) 
Neutrophil count decreased  1  1/80 (1.25%)  0/80 (0.00%) 
Blood creatinine increased  1  0/80 (0.00%)  1/80 (1.25%) 
Metabolism and nutrition disorders     
Dehydration  1  4/80 (5.00%)  3/80 (3.75%) 
Hypoalbuminaemia  1  1/80 (1.25%)  0/80 (0.00%) 
Hypoglycaemia  1  0/80 (0.00%)  1/80 (1.25%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/80 (1.25%)  0/80 (0.00%) 
Muscular weakness  1  0/80 (0.00%)  1/80 (1.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer  1  1/80 (1.25%)  0/80 (0.00%) 
Nervous system disorders     
Cerebral ischaemia  1  0/80 (0.00%)  1/80 (1.25%) 
Depressed level of consciousness  1  0/80 (0.00%)  1/80 (1.25%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  4/80 (5.00%)  2/80 (2.50%) 
Pneumonitis  1  2/80 (2.50%)  1/80 (1.25%) 
Pulmonary embolism  1  1/80 (1.25%)  2/80 (2.50%) 
Hypoxia  1  1/80 (1.25%)  0/80 (0.00%) 
Interstitial lung disease  1  1/80 (1.25%)  0/80 (0.00%) 
Oropharyngeal pain  1  1/80 (1.25%)  0/80 (0.00%) 
Respiratory failure  1  1/80 (1.25%)  0/80 (0.00%) 
Chronic obstructive pulmonary disease  1  0/80 (0.00%)  1/80 (1.25%) 
Vascular disorders     
Deep vein thrombosis  1  1/80 (1.25%)  3/80 (3.75%) 
Thrombosis  1  1/80 (1.25%)  0/80 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trametinib + Gemcitabine Placebo + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   80/80 (100.00%)   80/80 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  37/80 (46.25%)  34/80 (42.50%) 
Thrombocytopenia  1  32/80 (40.00%)  22/80 (27.50%) 
Neutropenia  1  28/80 (35.00%)  22/80 (27.50%) 
Leukopenia  1  9/80 (11.25%)  8/80 (10.00%) 
Lymphopenia  1  1/80 (1.25%)  5/80 (6.25%) 
Eye disorders     
Vision blurred  1  7/80 (8.75%)  10/80 (12.50%) 
Periorbital oedema  1  4/80 (5.00%)  0/80 (0.00%) 
Gastrointestinal disorders     
Nausea  1  43/80 (53.75%)  41/80 (51.25%) 
Vomiting  1  38/80 (47.50%)  36/80 (45.00%) 
Diarrhoea  1  43/80 (53.75%)  22/80 (27.50%) 
Constipation  1  23/80 (28.75%)  20/80 (25.00%) 
Stomatitis  1  29/80 (36.25%)  6/80 (7.50%) 
Abdominal pain  1  15/80 (18.75%)  14/80 (17.50%) 
Abdominal pain upper  1  9/80 (11.25%)  9/80 (11.25%) 
Abdominal distension  1  7/80 (8.75%)  8/80 (10.00%) 
Ascites  1  6/80 (7.50%)  8/80 (10.00%) 
Dyspepsia  1  8/80 (10.00%)  4/80 (5.00%) 
Flatulence  1  3/80 (3.75%)  7/80 (8.75%) 
Dry mouth  1  4/80 (5.00%)  5/80 (6.25%) 
Gingival bleeding  1  4/80 (5.00%)  0/80 (0.00%) 
Haemorrhoids  1  4/80 (5.00%)  0/80 (0.00%) 
General disorders     
Fatigue  1  30/80 (37.50%)  30/80 (37.50%) 
Oedema peripheral  1  30/80 (37.50%)  25/80 (31.25%) 
Pyrexia  1  27/80 (33.75%)  26/80 (32.50%) 
Asthenia  1  9/80 (11.25%)  13/80 (16.25%) 
Chills  1  8/80 (10.00%)  9/80 (11.25%) 
Mucosal inflammation  1  9/80 (11.25%)  4/80 (5.00%) 
Influenza like illness  1  1/80 (1.25%)  7/80 (8.75%) 
Pain  1  4/80 (5.00%)  3/80 (3.75%) 
Infections and infestations     
Urinary tract infection  1  2/80 (2.50%)  7/80 (8.75%) 
Paronychia  1  9/80 (11.25%)  0/80 (0.00%) 
Nasopharyngitis  1  4/80 (5.00%)  3/80 (3.75%) 
Cellulitis  1  1/80 (1.25%)  5/80 (6.25%) 
Investigations     
Platelet count decreased  1  22/80 (27.50%)  16/80 (20.00%) 
Alanine aminotransferase increased  1  12/80 (15.00%)  16/80 (20.00%) 
Aspartate aminotransferase increased  1  11/80 (13.75%)  12/80 (15.00%) 
Neutrophil count decreased  1  9/80 (11.25%)  14/80 (17.50%) 
Weight decreased  1  9/80 (11.25%)  9/80 (11.25%) 
Haemoglobin decreased  1  5/80 (6.25%)  7/80 (8.75%) 
Blood alkaline phosphatase increased  1  3/80 (3.75%)  11/80 (13.75%) 
Ejection fraction decreased  1  7/80 (8.75%)  2/80 (2.50%) 
White blood cell count decreased  1  0/80 (0.00%)  8/80 (10.00%) 
Blood creatinine increased  1  5/80 (6.25%)  0/80 (0.00%) 
Blood bilirubin increased  1  1/80 (1.25%)  4/80 (5.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  25/80 (31.25%)  25/80 (31.25%) 
Hypokalaemia  1  7/80 (8.75%)  7/80 (8.75%) 
Hypoalbuminaemia  1  9/80 (11.25%)  4/80 (5.00%) 
Dehydration  1  5/80 (6.25%)  4/80 (5.00%) 
Hyperglycaemia  1  1/80 (1.25%)  5/80 (6.25%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  5/80 (6.25%)  8/80 (10.00%) 
Myalgia  1  5/80 (6.25%)  3/80 (3.75%) 
Pain in extremity  1  2/80 (2.50%)  4/80 (5.00%) 
Nervous system disorders     
Dizziness  1  12/80 (15.00%)  11/80 (13.75%) 
Headache  1  6/80 (7.50%)  10/80 (12.50%) 
Dysgeusia  1  7/80 (8.75%)  7/80 (8.75%) 
Tremor  1  2/80 (2.50%)  6/80 (7.50%) 
Psychiatric disorders     
Depression  1  5/80 (6.25%)  9/80 (11.25%) 
Insomnia  1  8/80 (10.00%)  3/80 (3.75%) 
Anxiety  1  4/80 (5.00%)  5/80 (6.25%) 
Renal and urinary disorders     
Dysuria  1  4/80 (5.00%)  3/80 (3.75%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  13/80 (16.25%)  12/80 (15.00%) 
Cough  1  9/80 (11.25%)  6/80 (7.50%) 
Epistaxis  1  5/80 (6.25%)  2/80 (2.50%) 
Oropharyngeal pain  1  6/80 (7.50%)  2/80 (2.50%) 
Dyspnoea exertional  1  4/80 (5.00%)  2/80 (2.50%) 
Skin and subcutaneous tissue disorders     
Rash  1  38/80 (47.50%)  20/80 (25.00%) 
Alopecia  1  14/80 (17.50%)  10/80 (12.50%) 
Dermatitis acneiform  1  12/80 (15.00%)  4/80 (5.00%) 
Pruritus  1  4/80 (5.00%)  4/80 (5.00%) 
Acne  1  6/80 (7.50%)  1/80 (1.25%) 
Vascular disorders     
Deep vein thrombosis  1  6/80 (7.50%)  4/80 (5.00%) 
Hypotension  1  4/80 (5.00%)  6/80 (7.50%) 
Hypertension  1  2/80 (2.50%)  6/80 (7.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01231581     History of Changes
Other Study ID Numbers: 113487
First Submitted: August 30, 2010
First Posted: November 1, 2010
Results First Submitted: June 20, 2013
Results First Posted: September 26, 2013
Last Update Posted: September 26, 2013