An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01362296
• Collaborator: (none)
• Enrollment: 134
• Locations: 60
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase II, open-label, multicenter, randomized study to evaluate the efficacy and safety of GSK1120212 compared with docetaxel in the second line setting for subjects with locally advanced or metastatic (Stage IV) Non-small cell lung cancer (NSCLC) harboring a KRAS mutation who have failed one platinum-containing chemotherapy regimen. A small subset of NSCLC subjects harboring BRAF, NRAS, or MEK1 mutations will be randomized in addition to the primary KRAS population, for exploratory purposes.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer, Non-Small Cell	Drug: GSK1120212; Drug: docetaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open-label, Multicenter, Randomized Study to Assess the Efficacy and Safety of GSK1120212 Compared With Docetaxel in 2nd Line Subjects With Targeted Mutations (KRAS, NRAS, BRAF, MEK1) in Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC Stage IV)
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK1120212 Oral once daily	Drug: GSK1120212; Oral once daily
Active Comparator: docetaxel IV once every 3 weeks	Drug: docetaxel; IV once every 3 weeks

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) as Assessed by the Investigator (INV) [From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)]

   PFS is defined as the time from RAN until the earliest date of documented radiological PD or DT due to any cause. PD was assessed by the INV 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 (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. For participants (PAR) who did not have a documented date of PD or DT, PFS was censored at the date of the last adequate assessment. For PAR who received subsequent anti-cancer therapy prior to the date of documented PD or DT, PFS was censored at the date of the last adequate assessment prior to the initiation of therapy.

Secondary Outcome Measures

1. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)]

   Clinical chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G, G3, or G4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.

2. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)]

   Clinical chemistry parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any grade, Grade 3, or Grade 4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.

3. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)]

   Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.

4. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)]

   Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.

5. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)]

   Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).

6. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)]

   Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).

7. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)]

   Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, myelocytes, neutrophil bands (%). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).

8. Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)]

   Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, and myelocytes. Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).

9. Number of Participants With Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase [From randomization until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 19 months)]

   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 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

10. Number of Participants With Any SAE or Non-serious AE: Crossover Phase [From the date of the first dose of study treatment in the Crossover Phase until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 12 months)]

    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 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

11. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)]

    Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle thereafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

12. Change From Baseline in SBP and DBP: Crossover Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)]

    Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

13. Change From Baseline in Heart Rate: Randomized Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)]

    Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

14. Change From Baseline in Heart Rate: Crossover Phase [Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)]

    Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

15. Number of Participants With a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase [From randomization until the first documented evidence of a CR or PR (maximum of 10.2 months)]

    Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or PR (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]). Participants with unknown or missing response were treated as non-responders.

16. Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase [From the date of the first dose of study treatment in the Crossover Phase until the first documented evidence of a CR or PR (maximum of 4 months)]

    Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or PR (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]). Participants with unknown or missing response were treated as non-responders.

17. Duration of Response (DOR) as Assessed by the Investigator: Randomized Phase [Time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause (maximum of 10.2 months)]

    DOR was assessed by the investigator for participants with CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 mm in the short axis; without the appearance of new lesions) or PR (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]). DOR is defined as the time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation.

18. Overall Survival (OS) [Time interval between the date of randomization and the date of death due to any cause (maximum of 22 months)]

    OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, OS was censored at the date of last contact.

19. GSK1120212 Plasma Pharmacokinetic (PK) Concentration [Day 15 of Cycle 1: pre-dose; 0.5-2 hours, 2-4 hours, and 4-8 hours post-dose; Day 1 of Cycle 2, Cycle 3 and Cycle 4: pre-dose]

    Blood samples for PK analysis of GSK1120212 were collected at the following time points: Cycle 1 (Study Day 15), Cycle 2 (Study Day 22), Cycle 3 (Study Day 43), and Cycle 4 (Study Day 64). Post-dose PK samples collected on Day 15 of Cycle 1 occurred at least 1 hour apart. Participants were instructed to withhold the dose of GSK1120212 until after blood for PK samples had been drawn. Pre-dose samples were taken 15 minutes or less prior to taking the next dose (i.e., trough).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 18 years old with histologically- or cytologically-confirmed diagnosis of adenocarcinoma Stage IV NSCLC with a positive mutational status for the KRAS, NRAS, BRAF, or MEK1 gene.

• Documented tumor progression after receiving at least one, but not more than one, prior approved platinum-containing chemotherapy regimen for advanced stage/metastatic NSCLC.

• Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

• Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.

• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.

• Life expectancy of at least three months in the opinion of the investigator.

• Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization to study treatment and agree to use effective contraception. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the time of randomization to study medication until at least four weeks after the last dose of study treatment.

• Adequate baseline organ function.

Exclusion Criteria:

• History of another malignancy.

• Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.

• Treatment with a BRAF or MEK inhibitor or docetaxel as monotherapy or as part of a combination regimen.

• Anti-cancer therapy (including chemotherapy and radiation therapy) within the last three weeks.

• History or current evidence / risk of retinal vein occlusion or central serous retinopathy.

• Any current or history of tumor manifestation in the Central Nervous System.

• History or evidence of cardiovascular risk, including QTcB >=480 msec, uncontrolled arrhythmias, acute coronary syndrome, coronary angioplasty, or stenting within 6 months prior to randomization, >=Class II congestive heart failure, treatment refractory hypertension, intra-cardiac defibrillators or permanent pacemakers or cardiac metastases.

• Known Human Immunodeficiency Virus, Hepatitis B Virus (HBV), or Hepatitis C Virus (HBC) infection (with the exception of chronic or cleared HBV and HCV infection).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Scottsdale	Arizona	United States	85259
2	GSK Investigational Site	Orange	California	United States	92868
3	GSK Investigational Site	Aurora	Colorado	United States	80045
4	GSK Investigational Site	Jacksonville	Florida	United States	32224
5	GSK Investigational Site	Athens	Georgia	United States	30607
6	GSK Investigational Site	Coeur d'Alene	Idaho	United States	83814
7	GSK Investigational Site	Indianapolis	Indiana	United States	46202
8	GSK Investigational Site	Baltimore	Maryland	United States	21231-2410
9	GSK Investigational Site	Boston	Massachusetts	United States	02114
10	GSK Investigational Site	Boston	Massachusetts	United States	02215
11	GSK Investigational Site	Detroit	Michigan	United States	48201
12	GSK Investigational Site	Minneapolis	Minnesota	United States	55404
13	GSK Investigational Site	Rochester	Minnesota	United States	55905
14	GSK Investigational Site	St Louis	Missouri	United States	63110
15	GSK Investigational Site	Lebanon	New Hampshire	United States	03756
16	GSK Investigational Site	Durham	North Carolina	United States	27710
17	GSK Investigational Site	Columbus	Ohio	United States	43210
18	GSK Investigational Site	Portland	Oregon	United States	97239
19	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
20	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19141
21	GSK Investigational Site	Memphis	Tennessee	United States	38120
22	GSK Investigational Site	Austin	Texas	United States	78731
23	GSK Investigational Site	Houston	Texas	United States	77030
24	GSK Investigational Site	Fairfax	Virginia	United States	22031
25	GSK Investigational Site	Vancouver	Washington	United States	98684
26	GSK Investigational Site	Marseille cedex 20		France	13915
27	GSK Investigational Site	Paris Cedex 15		France	75908
28	GSK Investigational Site	Paris Cedex 20		France	75970
29	GSK Investigational Site	Paris cedex 5		France	75230
30	GSK Investigational Site	Strasbourg		France	67091
31	GSK Investigational Site	Toulouse Cedex 9		France	31059
32	GSK Investigational Site	Villejuif		France	94805
33	GSK Investigational Site	Athens		Greece	115 22
34	GSK Investigational Site	Athens		Greece	115 27
35	GSK Investigational Site	Heraklion, Crete		Greece	71110
36	GSK Investigational Site	Neo Faliro		Greece	18547
37	GSK Investigational Site	Thessaloniki		Greece	57010
38	GSK Investigational Site	Budapest		Hungary	1529
39	GSK Investigational Site	Székesfehérvár		Hungary	8000
40	GSK Investigational Site	Törökbálint		Hungary	2045
41	GSK Investigational Site	Genova	Liguria	Italy	16132
42	GSK Investigational Site	Milano	Lombardia	Italy	20133
43	GSK Investigational Site	Milano	Lombardia	Italy	20141
44	GSK Investigational Site	Seoul		Korea, Republic of	110-744
45	GSK Investigational Site	Seoul		Korea, Republic of	120-752
46	GSK Investigational Site	Seoul		Korea, Republic of	135-710
47	GSK Investigational Site	Seoul		Korea, Republic of	138-736
48	GSK Investigational Site	Amsterdam		Netherlands	1066 CX
49	GSK Investigational Site	Amsterdam		Netherlands	1081 HV
50	GSK Investigational Site	Breda		Netherlands	4818 CK
51	GSK Investigational Site	Groningen		Netherlands	9713 GZ
52	GSK Investigational Site	Maastricht		Netherlands	6229 HX
53	GSK Investigational Site	Zwolle		Netherlands	8011 JW
54	GSK Investigational Site	Badalona		Spain	08916
55	GSK Investigational Site	Barcelona		Spain	08035
56	GSK Investigational Site	Madrid		Spain	28034
57	GSK Investigational Site	Madrid		Spain	28041
58	GSK Investigational Site	Madrid		Spain	28050
59	GSK Investigational Site	Majadahonda (Madrid)		Spain	28222
60	GSK Investigational Site	Pamplona		Spain	31008

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01362296
• Other Study ID Numbers: 114653
• First Posted: May 30, 2011
• Last Update Posted: Jul 11, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by GlaxoSmithKline: NRAS; docetaxel; NSCLC; GSK1120212; MEK inhibitor; targeted therapy; KRAS; BRAF
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Trametinib

Study Results

Participant Flow

Recruitment Details	Participants who met eligibility criteria at Screening were then randomized to the treatment period. A total of 134 participants were randomized, and 130 participants entered the treatment period.
Pre-assignment Detail	In the Randomized Phase (RP), participants were treated until disease progression (PD), death, or unacceptable adverse events were experienced. After PD in the RP, participants were given the option of crossing over to the alternative treatment arm in a Cross-over Phase (CP).

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Period Title: Randomized Phase (RP)
STARTED	87	43	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	87	43	0	0
Period Title: Randomized Phase (RP)
STARTED	0	0	23	2
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	23	2

Baseline Characteristics

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP	Total
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.	Total of all reporting groups
Overall Participants	89	45	134
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.4 (8.97)	60.9 (10.06)	61.2 (9.32)
Sex: Female, Male (Count of Participants)
Female	43 48.3%	22 48.9%	65 48.5%
Male	46 51.7%	23 51.1%	69 51.5%
Race/Ethnicity, Customized (Number) [Number]
White - White/Caucasian/European Heritage	73 82%	32 71.1%	105 78.4%
Asian - East Asian Heritage	11 12.4%	9 20%	20 14.9%
White - Arabic/North African Heritage	1 1.1%	3 6.7%	4 3%
African American/African Heritage	3 3.4%	0 0%	3 2.2%
Asian - South East Asian Heritage	0 0%	1 2.2%	1 0.7%
Missing	1 1.1%	0 0%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) as Assessed by the Investigator (INV)
Description	PFS is defined as the time from RAN until the earliest date of documented radiological PD or DT due to any cause. PD was assessed by the INV 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 (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. For participants (PAR) who did not have a documented date of PD or DT, PFS was censored at the date of the last adequate assessment. For PAR who received subsequent anti-cancer therapy prior to the date of documented PD or DT, PFS was censored at the date of the last adequate assessment prior to the initiation of therapy.
Time Frame	From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (MITT) Population: all randomized participants with KRAS mutation-positive non-small cell lung cancer (NSCLC), whether or not treatment was administered

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	86	43
Median (95% Confidence Interval) [Weeks]	11.7	11.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1120212 2 mg in RP, Docetaxel 75 mg/m^2 in RP
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5197
	Comments	P-value from the stratified log-rank was adjusted for gender (male versus female).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments	HRs were estimated using a Pike estimator. The HR from the stratified log-rank test was adjusted for gender (male versus female).

2. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase
Description	Clinical chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G, G3, or G4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Outcome Measure Data

Analysis Population Description

Safety Population: all participants (KRAS, BRAF, NRAS, and MEK1 mutation positive) that received at least one dose of study treatment, based on the actual treatment received if this differed from that to which the participant was randomized. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	87	43
Albumin, Increase to any G (IAG), n=86, 43	57 64%	21 46.7%
Albumin, Increase to G3, n=86, 43	4 4.5%	1 2.2%
Albumin, Increase to G4, n=86, 43	0 0%	0 0%
ALKP, IAG, n=85, 43	26 29.2%	3 6.7%
ALKP, Increase to G3, n =85, 43	2 2.2%	1 2.2%
ALKP, Increase to G4, n=85, 43	0 0%	0 0%
ALT, IAG, n=87, 43	32 36%	7 15.6%
ALT, Increase to G3, n=87, 43	3 3.4%	1 2.2%
ALT, Increase to G4, n=87, 43	0 0%	0 0%
AST, IAG, n=86, 43	55 61.8%	11 24.4%
AST, Increase to G3, n=86, 43	1 1.1%	0 0%
AST, Increase to G4, n=86, 43	0 0%	0 0%
Total bilirubin, IAG, n=85, 42	3 3.4%	3 6.7%
Total bilirubin, Increase to G3, n=85, 42	0 0%	0 0%
Total bilirubin, Increase to G4, n=85, 42	0 0%	0 0%
Calcium (hypercalcemia), IAG, n =87, 43	9 10.1%	3 6.7%
Calcium (hypercalcemia), Increase to G3, n=87, 43	0 0%	0 0%
Calcium (hypercalcemia), Increase to G4, n=87, 43	0 0%	0 0%
Calcium (hypocalcemia), IAG, n=87, 43	4 4.5%	1 2.2%
Calcium (hypocalcemia), Increase to G3, n=87, 43	0 0%	1 2.2%
Calcium (hypocalcemia), Increase to G4, n=87, 43	1 1.1%	0 0%
Creatine kinase, IAG, n=1, 0	0 0%	0 0%
Creatine kinase, Increase to G3, n=1, 0	0 0%	0 0%
Creatine kinase, Increase to G4, n=1, 0	0 0%	0 0%
Creatinine, IAG, n=87, 43	12 13.5%	6 13.3%
Creatinine, Increase to G3, n=87, 43	3 3.4%	1 2.2%
Creatinine, Increase to G4, n=87, 43	0 0%	0 0%
Glucose (hyperglycemia), IAG, n=87, 43	47 52.8%	24 53.3%
Glucose (hyperglycemia), Increase to G3, n=87, 43	5 5.6%	2 4.4%
Glucose (hyperglycemia), Increase to G4, n=87, 43	0 0%	0 0%
Glucose (hypoglycemia), IAG, n=87, 43	4 4.5%	4 8.9%
Glucose (hypoglycemia), Increase to G3, n=87, 43	0 0%	0 0%
Glucose (hypoglycemia), Increase to G4, n=87, 43	0 0%	0 0%
Potassium (hyperkalemia), IAG, n=86,	9 10.1%	4 8.9%
Potassium (hyperkalemia), Increase to G3, n=86, 43	1 1.1%	1 2.2%
Potassium (hyperkalemia), Increase to G4, n=86, 43	0 0%	0 0%
Potassium (hypokalemia), IAG, n=86, 43	8 9%	2 4.4%
Potassium (hypokalemia), Increase to G3, n=86, 43	0 0%	0 0%
Potassium (hypokalemia), Increase to G4, n=86, 43	0 0%	0 0%
Sodium (hypernatremia), IAG, n=87, 43	12 13.5%	2 4.4%
Sodium (hypernatremia), Increase to G3, n=87, 43	0 0%	0 0%
Sodium (hypernatremia), Increase to G4, n=87, 43	0 0%	0 0%
Sodium (hyponatremia), IAG, n=87, 43	16 18%	5 11.1%
Sodium (hyponatremia), Increase to G3, n=87, 43	2 2.2%	1 2.2%
Sodium (hyponatremia), Increase to G4, n=87, 43	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase
Description	Clinical chemistry parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any grade, Grade 3, or Grade 4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Outcome Measure Data

Analysis Population Description

Crossover Population: all participants who, at the point of disease progression during the Randomized Phase, elected to enter the crossover portion of the study. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	1
Albumin, Increase to any G (IAG), n=23, 1	15 16.9%	1 2.2%
Albumin, Increase to G3, n=23, 1	4 4.5%	0 0%
Albumin, Increase to G4, n=23, 1	0 0%	0 0%
ALKP, IAG, n=23, 1	10 11.2%	0 0%
ALKP, Increase to G3, n =23, 1	1 1.1%	0 0%
ALKP, Increase to G4, n=23, 1	0 0%	0 0%
ALT, IAG, n=23, 1	7 7.9%	0 0%
ALT, Increase to G3, n=23, 1	1 1.1%	0 0%
ALT, Increase to G4, n=23, 1	0 0%	0 0%
AST, IAG, n=23, 1	9 10.1%	0 0%
AST, Increase to G3, n=23, 1	1 1.1%	0 0%
AST, Increase to G4, n=23, 1	0 0%	0 0%
Total bilirubin, IAG, n=22, 1	1 1.1%	0 0%
Total bilirubin, Increase to G3, n=22, 1	0 0%	0 0%
Total bilirubin, Increase to G4, n=22, 1	0 0%	0 0%
Calcium (hypercalcemia), IAG, n =23, 1	1 1.1%	0 0%
Calcium (hypercalcemia), Increase to G3, n=23, 1	0 0%	0 0%
Calcium (hypercalcemia), Increase to G4, n=23, 1	0 0%	0 0%
Calcium (hypocalcemia), IAG, n=23, 1	0 0%	0 0%
Calcium (hypocalcemia), Increase to G3, n=23, 1	0 0%	0 0%
Calcium (hypocalcemia), Increase to G4, n=23, 1	0 0%	0 0%
Creatine kinase, IAG, n=1, 0	1 1.1%	0 0%
Creatine kinase, Increase to G3, n=1, 0	0 0%	0 0%
Creatine kinase, Increase to G4, n=1, 0	0 0%	0 0%
Creatinine, IAG, n=23, 1	3 3.4%	0 0%
Creatinine, Increase to G3, n=23, 1	0 0%	0 0%
Creatinine, Increase to G4, n=23, 1	0 0%	0 0%
Glucose (hyperglycemia), IAG, n=23, 1	10 11.2%	0 0%
Glucose (hyperglycemia), Increase to G3, n=23, 1	0 0%	0 0%
Glucose (hyperglycemia), Increase to G4, n=23, 1	0 0%	0 0%
Glucose (hypoglycemia), IAG, n=23, 1	1 1.1%	0 0%
Glucose (hypoglycemia), Increase to G3, n=23, 1	0 0%	0 0%
Glucose (hypoglycemia), Increase to G4, n=23, 1	0 0%	0 0%
Potassium (hyperkalemia), IAG, n=23, 1	3 3.4%	0 0%
Potassium (hyperkalemia), Increase to G3, n=23, 1	1 1.1%	0 0%
Potassium (hyperkalemia), Increase to G4, n=23, 1	0 0%	0 0%
Potassium (hypokalemia), IAG, n=23, 1	1 1.1%	0 0%
Potassium (hypokalemia), Increase to G3, n=23, 1	0 0%	0 0%
Potassium (hypokalemia), Increase to G4, n=23, 1	0 0%	0 0%
Sodium (hypernatremia), IAG, n=23, 1	1 1.1%	0 0%
Sodium (hypernatremia), Increase to G3, n=23, 1	0 0%	0 0%
Sodium (hypernatremia), Increase to G4, n=23, 1	0 0%	0 0%
Sodium (hyponatremia), IAG, n=23, 1	3 3.4%	0 0%
Sodium (hyponatremia), Increase to G3, n=23, 1	2 2.2%	0 0%
Sodium (hyponatremia), Increase to G4, n=23, 1	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase
Description	Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	87	43
Haemoglobin (inc), IAG, n=87, 43	0 0%	0 0%
Haemoglobin (inc), Increase to G3, n=87, 43	0 0%	0 0%
Haemoglobin (inc), Increase to G4, n=87, 43	0 0%	0 0%
Haemoglobin (anemia), IAG, n=86, 43	34 38.2%	27 60%
Haemoglobin (anemia), Increase to G3, n=86, 43	8 9%	3 6.7%
Haemoglobin (anemia), Increase to G4, n=86, 43	0 0%	0 0%
Lymphocyte ct (inc), IAG, n=86, 43	9 10.1%	2 4.4%
Lymphocyte ct (inc), Increase to G3, n=86, 43	1 1.1%	0 0%
Lymphocyte ct (inc), Increase to G4, n=86, 43	0 0%	0 0%
Lymphocyte ct (dec), IAG, n=85, 43	18 20.2%	19 42.2%
Lymphocyte ct (dec), Increase to G3, n=85, 43	4 4.5%	2 4.4%
Lymphocyte ct (dec), Increase to G4, n=85, 43	0 0%	0 0%
ANC, IAG, n=86, 43	5 5.6%	34 75.6%
ANC, Increase to G3, n=86, 43	0 0%	13 28.9%
ANC, Increase to G4, n=86, 43	0 0%	13 28.9%
Platelet ct, IAG, n=87, 43	15 16.9%	3 6.7%
Platelet ct, Increase to G3, n=87, 43	0 0%	0 0%
Platelet ct, Increase to G4, n=87, 43	0 0%	0 0%
WBC, IAG, n=87, 43	5 5.6%	33 73.3%
WBC, Increase to G3, n=87, 43	0 0%	17 37.8%
WBC, Increase to G4, n=87, 43	1 1.1%	0 0%

5. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase
Description	Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Outcome Measure Data

Analysis Population Description

Crossover Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	1
Haemoglobin (inc), IAG, n=23, 1	0 0%	0 0%
Haemoglobin (inc), Increase to G3, n=23, 1	0 0%	0 0%
Haemoglobin (inc), Increase to G4, n=23, 1	0 0%	0 0%
Haemoglobin (anemia), IAG, n=23, 1	12 13.5%	0 0%
Haemoglobin (anemia), Increase to G3, n=23, 1	2 2.2%	0 0%
Haemoglobin (anemia), Increase to G4, n=23, 1	0 0%	0 0%
Lymphocyte ct (inc), IAG, n=23, 1	1 1.1%	0 0%
Lymphocyte ct (inc), Increase to G3, n=23, 1	0 0%	0 0%
Lymphocyte ct (inc), Increase to G4, n=23, 1	0 0%	0 0%
Lymphocyte ct (dec), IAG, n=23, 1	3 3.4%	0 0%
Lymphocyte ct (dec), Increase to G3, n=23, 1	0 0%	0 0%
Lymphocyte ct (dec), Increase to G4, n=23, 1	0 0%	0 0%
ANC, IAG, n=19, 0	0 0%	0 0%
ANC, Increase to G3, n=19, 0	0 0%	0 0%
ANC, Increase to G4, n=19, 0	0 0%	0 0%
Platelet ct, IAG, n=23, 1	4 4.5%	0 0%
Platelet ct, Increase to G3, n=23, 1	0 0%	0 0%
Platelet ct, Increase to G4, n=23, 1	0 0%	0 0%
WBC, IAG, n=23, 1	0 0%	0 0%
WBC, Increase to G3, n=23, 1	0 0%	0 0%
WBC, Increase to G4, n=23, 1	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase
Description	Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	87	43
Lactate dehydrogenase, Decrease to low, n=87, 43	1 1.1%	0 0%
Lactate dehydrogenase, CTN or no change, n=87, 43	40 44.9%	23 51.1%
Lactate dehydrogenase, Increase to high, n=87, 43	46 51.7%	20 44.4%
Total Protein, Decrease to low, n=86, 43	31 34.8%	12 26.7%
Total Protein, CTN or no change, n=86, 43	55 61.8%	31 68.9%
Total Protein, Increase to high, n=86, 43	1 1.1%	0 0%
Urea/BUN, Decrease to low, n=87, 43	0 0%	0 0%
Urea/BUN, CTN or no change, n=87, 43	62 69.7%	34 75.6%
Urea/BUN, Increase to high, n=87,43	25 28.1%	9 20%

7. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase
Description	Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Outcome Measure Data

Analysis Population Description

Crossover Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	1
Lactate dehydrogenase, Decrease to low	0 0%	0 0%
Lactate dehydrogenase, CTN or no change	15 16.9%	1 2.2%
Lactate dehydrogenase, Increase to high	8 9%	0 0%
Total Protein, Decrease to low	15 16.9%	0 0%
Total Protein, CTN or no change	8 9%	1 2.2%
Total Protein, Increase to high	0 0%	0 0%
Urea/BUN, Decrease to low	0 0%	0 0%
Urea/BUN, CTN or no change	18 20.2%	1 2.2%
Urea/BUN, Increase to high	5 5.6%	0 0%

8. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase
Description	Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, myelocytes, neutrophil bands (%). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	86	43
Atypical lymphs, Decrease to low, n=0, 3	0 0%	0 0%
Atypical lymphs, CTN or no change, n=0, 3	0 0%	0 0%
Atypical lymphs, Increase to high, n=0, 3	0 0%	3 6.7%
Atypical lymphs (%), Decrease to low, n =0, 3	0 0%	0 0%
Atypical lymphs (%), CTN or no change, n=0, 3	0 0%	0 0%
Atypical lymphs (%), Increase to high, n=0, 3	0 0%	3 6.7%
Basophils, Decrease to low, n=86, 43	0 0%	0 0%
Basophils, CTN or no change, n=86, 43	82 92.1%	41 91.1%
Basophils, Increase to high, n=86,43	4 4.5%	2 4.4%
Eosinophils, Decrease to low, n=86, 43	1 1.1%	1 2.2%
Eosinophils, CTN or no change, n=86, 43	77 86.5%	42 93.3%
Eosinophils, Increase to high, n=86, 43	9 10.1%	0 0%
Metamyelocytes, Decrease to low, n=1, 7	0 0%	0 0%
Metamyelocytes, CTN or no change, n=1, 7	0 0%	0 0%
Metamyelocytes, Increase to high, n=1, 7	1 1.1%	7 15.6%
Monocytes, Decrease to low, n=86, 43	3 3.4%	20 44.4%
Monocytes, CTN or no change, n=86, 43	78 87.6%	18 40%
Monocytes, Increase to high, n=86, 43	5 5.6%	9 20%
Myelocytes, Decrease to low, n=1, 9	0 0%	0 0%
Myelocytes, CTN or no change, n=1, 9	0 0%	1 2.2%
Myelocytes, Increase to high, n=1, 9	1 1.1%	8 17.8%
Neutrophil Bands (%), Decrease to low, n=1, 4	0 0%	0 0%
Neutrophil Bands (%), CTN or no change, n=1, 4	1 1.1%	3 6.7%
Neutrophil Bands (%), Increase to high, n=1, 4	0 0%	1 2.2%

9. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase
Description	Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, and myelocytes. Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Outcome Measure Data

Analysis Population Description

Crossover Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	1
Atypical lymphs, Decrease to low, n=3, 1	0 0%	0 0%
Atypical lymphs, CTN or no change, n=3, 1	1 1.1%	0 0%
Atypical lymphs, Increase to high, n=3, 1	2 2.2%	1 2.2%
Atypical lymphs (%), Decrease to low, n=3, 1	0 0%	0 0%
Atypical lymphs (%), CTN or no change, n=3, 1	1 1.1%	0 0%
Atypical lymphs (%), Increase to high, n=3, 1	2 2.2%	1 2.2%
Basophils, Decrease to low, n=23, 1	0 0%	0 0%
Basophils, CTN or no change, n=23, 1	23 25.8%	1 2.2%
Basophils, Increase to high, n=23, 1	0 0%	0 0%
Eosinophils, Decrease to low, n=23, 1	0 0%	0 0%
Eosinophils, CTN or no change, n=23, 1	23 25.8%	1 2.2%
Eosinophils, Increase to high, n=23, 1	0 0%	0 0%
Metamyelocytes, Decrease to low, n=1, 1	0 0%	0 0%
Metamyelocytes, CTN or no change, n=1, 1	0 0%	0 0%
Metamyelocytes, Increase to high, n=1, 1	1 1.1%	1 2.2%
Monocytes, Decrease to low, n=23, 1	1 1.1%	0 0%
Monocytes, CTN or no change, n=23, 1	20 22.5%	0 0%
Monocytes, Increase to high, n=23, 1	2 2.2%	1 2.2%
Myelocytes, Decrease to low, n=3, 1	0 0%	0 0%
Myelocytes, CTN or no change, n=3, 1	0 0%	0 0%
Myelocytes, Increase to high, n=3, 1	3 3.4%	1 2.2%

10. Secondary Outcome

Title	Number of Participants With Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase
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 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame	From randomization until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 19 months)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	87	43
Any AE	87 97.8%	43 95.6%
Any SAE	32 36%	9 20%

11. Secondary Outcome

Title	Number of Participants With Any SAE or Non-serious AE: Crossover Phase
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 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame	From the date of the first dose of study treatment in the Crossover Phase until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 12 months)

Outcome Measure Data

Analysis Population Description

Crossover Population

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	2
Any AE	22 24.7%	2 4.4%
Any SAE	12 13.5%	1 2.2%

12. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase
Description	Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle thereafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	87	43
SBP, Worst-case on-therapy	13.5 (16.63)	3.1 (13.71)
DBP, Worst-case on-therapy	10.7 (9.95)	2.5 (7.34)

13. Secondary Outcome

Title	Change From Baseline in SBP and DBP: Crossover Phase
Description	Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Outcome Measure Data

Analysis Population Description

Crossover Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	1
SBP, Worst-case on-therapy	8.7 (15.95)	-15.0 (NA)
DBP, Worst-case on-therapy	8.3 (12.28)	-12.0 (NA)

14. Secondary Outcome

Title	Change From Baseline in Heart Rate: Randomized Phase
Description	Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	87	43
Mean (Standard Deviation) [Beats per minute]	10.4 (14.23)	13.2 (9.31)

15. Secondary Outcome

Title	Change From Baseline in Heart Rate: Crossover Phase
Description	Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame	Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Outcome Measure Data

Analysis Population Description

Crossover Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	1
Mean (Standard Deviation) [Beats per minute]	8.5 (11.46)	5.0 (NA)

16. Secondary Outcome

Title	Number of Participants With a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase
Description	Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or PR (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]). Participants with unknown or missing response were treated as non-responders.
Time Frame	From randomization until the first documented evidence of a CR or PR (maximum of 10.2 months)

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	86	43
CR	0 0%	0 0%
PR	10 11.2%	5 11.1%

17. Secondary Outcome

Title	Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase
Description	Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or PR (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]). Participants with unknown or missing response were treated as non-responders.
Time Frame	From the date of the first dose of study treatment in the Crossover Phase until the first documented evidence of a CR or PR (maximum of 4 months)

Outcome Measure Data

Analysis Population Description

Crossover Population

Arm/Group Title	GSK1120212 2 mg in CP	Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	23	2
CR	0 0%	0 0%
PR	1 1.1%	0 0%

18. Secondary Outcome

Title	Duration of Response (DOR) as Assessed by the Investigator: Randomized Phase
Description	DOR was assessed by the investigator for participants with CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 mm in the short axis; without the appearance of new lesions) or PR (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]). DOR is defined as the time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
Time Frame	Time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause (maximum of 10.2 months)

Outcome Measure Data

Analysis Population Description

MITT Population. Only participants who achieved a CR or PR were analyzed for duration of response.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	10	5
Mean (95% Confidence Interval) [Weeks]	6.7	12.4

19. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, OS was censored at the date of last contact.
Time Frame	Time interval between the date of randomization and the date of death due to any cause (maximum of 22 months)

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	86	43
Median (95% Confidence Interval) [Months]	8.1	9.9

20. Secondary Outcome

Title	GSK1120212 Plasma Pharmacokinetic (PK) Concentration
Description	Blood samples for PK analysis of GSK1120212 were collected at the following time points: Cycle 1 (Study Day 15), Cycle 2 (Study Day 22), Cycle 3 (Study Day 43), and Cycle 4 (Study Day 64). Post-dose PK samples collected on Day 15 of Cycle 1 occurred at least 1 hour apart. Participants were instructed to withhold the dose of GSK1120212 until after blood for PK samples had been drawn. Pre-dose samples were taken 15 minutes or less prior to taking the next dose (i.e., trough).
Time Frame	Day 15 of Cycle 1: pre-dose; 0.5-2 hours, 2-4 hours, and 4-8 hours post-dose; Day 1 of Cycle 2, Cycle 3 and Cycle 4: pre-dose

Outcome Measure Data

Analysis Population Description

PK Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK1120212 2 mg in RP	Docetaxel 75 mg/m^2 in RP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).	Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Measure Participants	80	0
Cycle 1, Day 15, pre-dose, n=80	16.1 (5.31)
Cycle 1, Day 15, 0.5-2 hours post-dose, n=78	21.5 (8.59)
Cycle 1, Day 15, 2-4 hours post-dose, n=77	29.7 (22.9)
Cycle 1, Day 15, 4-8 hours post-dose, n=78	24.8 (7.80)
Cycle 2, Day 1, pre-dose, n=75	16.7 (6.95)
Cycle 3, Day 1, pre-dose, n=60	12.9 (7.19)
Cycle 4, Day 1, pre-dose, n=38	13.9 (6.49)

Adverse Events

Time Frame	Serious Adverse Events (SAEs) and non-serious AEs were collected from the first dose of study treatment until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy (maximum of 19 months).
Adverse Event Reporting Description	SAEs and non-serious AEs were collected in members of the Safety Population (all participants who received at least one dose of study treatment) and the Crossover Population (participants who, at the point of disease progression during the Randomized Phase, elected to enter the crossover portion of the study).
Arm/Group Title	GSK1120212 2 mg in RP		Docetaxel 75 mg/m^2 in RP		GSK1120212 2 mg in CP		Docetaxel 75 mg/m^2 in CP
Arm/Group Description	Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced.		Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced.		Participants who experienced disease progression in the RP were given the option of crossing over to GSK1120212 2 mg and continuing in the Cross-over Phase (CP).		Participants who experienced disease progression in the RP were given the option of crossing over to docetaxel 75 mg/m^2 and continuing in the CP.
All Cause Mortality
	GSK1120212 2 mg in RP		Docetaxel 75 mg/m^2 in RP		GSK1120212 2 mg in CP		Docetaxel 75 mg/m^2 in CP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	GSK1120212 2 mg in RP		Docetaxel 75 mg/m^2 in RP		GSK1120212 2 mg in CP		Docetaxel 75 mg/m^2 in CP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/87 (36.8%)		9/43 (20.9%)		12/23 (52.2%)		1/2 (50%)
Blood and lymphatic system disorders
Febrile neutropenia	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		1/2 (50%)
Neutropenia	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Cardiac disorders
Atrial fibrillation	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Gastrointestinal disorders
Diarrhoea	2/87 (2.3%)		1/43 (2.3%)		1/23 (4.3%)		0/2 (0%)
Vomiting	2/87 (2.3%)		1/43 (2.3%)		1/23 (4.3%)		0/2 (0%)
Abdominal pain	1/87 (1.1%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Colitis	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Gastric ulcer perforation	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Gastrointestinal haemorrhage	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Sigmoiditis	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
General disorders
Pyrexia	3/87 (3.4%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Oedema	2/87 (2.3%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Death	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
General physical health deterioration	0/87 (0%)		0/43 (0%)		2/23 (8.7%)		0/2 (0%)
Infections and infestations
Pneumonia	6/87 (6.9%)		1/43 (2.3%)		2/23 (8.7%)		0/2 (0%)
Sepsis	4/87 (4.6%)		1/43 (2.3%)		2/23 (8.7%)		0/2 (0%)
Pneumocystis jiroveci infection	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Septic shock	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Bronchitis	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Bronchitis bacterial	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Cellulitis	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Gastroenteritis	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Lung infection	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Rash pustular	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Injury, poisoning and procedural complications
Radiation pneumonitis	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Spinal compression fracture	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Pubis fracture	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Investigations
Hepatic enzyme increased	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Metabolism and nutrition disorders
Dehydration	2/87 (2.3%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Hypoalbuminaemia	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Hyponatraemia	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Pain in extremity	0/87 (0%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Nervous system disorders
Transient ischaemic attack	2/87 (2.3%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Ischaemic stroke	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Loss of consciousness	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Somnolence	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Renal and urinary disorders
Renal failure acute	2/87 (2.3%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Haematuria	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/87 (2.3%)		1/43 (2.3%)		1/23 (4.3%)		0/2 (0%)
Pulmonary embolism	2/87 (2.3%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Acute respiratory failure	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Bronchospasm	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Haemoptysis	1/87 (1.1%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Pneumonitis	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Pulmonary hypertension	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Pleural effusion	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Respiratory failure	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Rash	2/87 (2.3%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Dermatitis exfoliative	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Palmar-plantar erythrodysaesthesia syndrome	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Rash generalised	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Angioedema	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Vascular disorders
Thrombosis	2/87 (2.3%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Embolism	1/87 (1.1%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Venous thrombosis	1/87 (1.1%)		0/43 (0%)		1/23 (4.3%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	GSK1120212 2 mg in RP		Docetaxel 75 mg/m^2 in RP		GSK1120212 2 mg in CP		Docetaxel 75 mg/m^2 in CP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	87/87 (100%)		43/43 (100%)		20/23 (87%)		1/2 (50%)
Blood and lymphatic system disorders
Anaemia	18/87 (20.7%)		8/43 (18.6%)		5/23 (21.7%)		0/2 (0%)
Neutropenia	0/87 (0%)		15/43 (34.9%)		0/23 (0%)		0/2 (0%)
Leukopenia	0/87 (0%)		5/43 (11.6%)		0/23 (0%)		0/2 (0%)
Eye disorders
Lacrimation increased	3/87 (3.4%)		3/43 (7%)		0/23 (0%)		0/2 (0%)
Gastrointestinal disorders
Diarrhoea	44/87 (50.6%)		9/43 (20.9%)		11/23 (47.8%)		1/2 (50%)
Nausea	30/87 (34.5%)		12/43 (27.9%)		5/23 (21.7%)		0/2 (0%)
Constipation	18/87 (20.7%)		7/43 (16.3%)		5/23 (21.7%)		0/2 (0%)
Vomiting	20/87 (23%)		5/43 (11.6%)		5/23 (21.7%)		0/2 (0%)
Dry mouth	13/87 (14.9%)		1/43 (2.3%)		3/23 (13%)		0/2 (0%)
Abdominal pain upper	9/87 (10.3%)		2/43 (4.7%)		0/23 (0%)		0/2 (0%)
Stomatitis	8/87 (9.2%)		3/43 (7%)		0/23 (0%)		0/2 (0%)
Abdominal pain	5/87 (5.7%)		3/43 (7%)		1/23 (4.3%)		1/2 (50%)
Gastritis	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		1/2 (50%)
General disorders
Fatigue	24/87 (27.6%)		12/43 (27.9%)		0/23 (0%)		0/2 (0%)
Asthenia	20/87 (23%)		11/43 (25.6%)		4/23 (17.4%)		1/2 (50%)
Oedema peripheral	19/87 (21.8%)		5/43 (11.6%)		7/23 (30.4%)		0/2 (0%)
Pyrexia	15/87 (17.2%)		4/43 (9.3%)		3/23 (13%)		0/2 (0%)
Mucosal inflammation	6/87 (6.9%)		6/43 (14%)		0/23 (0%)		0/2 (0%)
Face oedema	6/87 (6.9%)		2/43 (4.7%)		0/23 (0%)		0/2 (0%)
Oedema	6/87 (6.9%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Chills	6/87 (6.9%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Infections and infestations
Paronychia	7/87 (8%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Lung infection	0/87 (0%)		0/43 (0%)		0/23 (0%)		1/2 (50%)
Urinary tract infection	5/87 (5.7%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Investigations
Weight decreased	7/87 (8%)		2/43 (4.7%)		0/23 (0%)		0/2 (0%)
Aspartate aminotransferase increased	6/87 (6.9%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Neutrophil count decreased	0/87 (0%)		7/43 (16.3%)		0/23 (0%)		0/2 (0%)
Alanine aminotransferase increased	3/87 (3.4%)		3/43 (7%)		0/23 (0%)		0/2 (0%)
Ejection fraction decreased	5/87 (5.7%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
White blood cell count decreased	0/87 (0%)		3/43 (7%)		0/23 (0%)		0/2 (0%)
Metabolism and nutrition disorders
Decreased appetite	21/87 (24.1%)		7/43 (16.3%)		5/23 (21.7%)		0/2 (0%)
Hypoalbuminaemia	9/87 (10.3%)		1/43 (2.3%)		4/23 (17.4%)		0/2 (0%)
Hyperglycaemia	5/87 (5.7%)		2/43 (4.7%)		0/23 (0%)		0/2 (0%)
Dehydration	5/87 (5.7%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Hypokalaemia	5/87 (5.7%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	6/87 (6.9%)		10/43 (23.3%)		0/23 (0%)		0/2 (0%)
Back pain	8/87 (9.2%)		6/43 (14%)		2/23 (8.7%)		1/2 (50%)
Arthralgia	3/87 (3.4%)		5/43 (11.6%)		0/23 (0%)		0/2 (0%)
Muscular weakness	0/87 (0%)		0/43 (0%)		1/23 (4.3%)		1/2 (50%)
Nervous system disorders
Dizziness	6/87 (6.9%)		5/43 (11.6%)		2/23 (8.7%)		0/2 (0%)
Neuropathy peripheral	2/87 (2.3%)		9/43 (20.9%)		0/23 (0%)		0/2 (0%)
Dysgeusia	3/87 (3.4%)		5/43 (11.6%)		0/23 (0%)		0/2 (0%)
Paraesthesia	1/87 (1.1%)		3/43 (7%)		0/23 (0%)		0/2 (0%)
Headache	5/87 (5.7%)		2/43 (4.7%)		0/23 (0%)		0/2 (0%)
Psychiatric disorders
Insomnia	6/87 (6.9%)		9/43 (20.9%)		0/23 (0%)		0/2 (0%)
Confusional state	5/87 (5.7%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Anxiety	2/87 (2.3%)		3/43 (7%)		1/23 (4.3%)		1/2 (50%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	28/87 (32.2%)		7/43 (16.3%)		4/23 (17.4%)		1/2 (50%)
Cough	24/87 (27.6%)		7/43 (16.3%)		6/23 (26.1%)		0/2 (0%)
Haemoptysis	7/87 (8%)		1/43 (2.3%)		0/23 (0%)		0/2 (0%)
Oropharyngeal pain	3/87 (3.4%)		4/43 (9.3%)		0/23 (0%)		0/2 (0%)
Productive cough	2/87 (2.3%)		5/43 (11.6%)		0/23 (0%)		0/2 (0%)
Epistaxis	6/87 (6.9%)		0/43 (0%)		2/23 (8.7%)		0/2 (0%)
Pleural effusion	0/87 (0%)		0/43 (0%)		2/23 (8.7%)		0/2 (0%)
Pulmonary embolism	0/87 (0%)		0/43 (0%)		0/23 (0%)		1/2 (50%)
Dyspnoea exertional	0/87 (0%)		3/43 (7%)		0/23 (0%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Rash	50/87 (57.5%)		6/43 (14%)		7/23 (30.4%)		0/2 (0%)
Alopecia	2/87 (2.3%)		17/43 (39.5%)		0/23 (0%)		0/2 (0%)
Pruritus	17/87 (19.5%)		2/43 (4.7%)		0/23 (0%)		0/2 (0%)
Dry skin	15/87 (17.2%)		2/43 (4.7%)		3/23 (13%)		0/2 (0%)
Dermatitis acneiform	11/87 (12.6%)		2/43 (4.7%)		2/23 (8.7%)		0/2 (0%)
Skin fissures	8/87 (9.2%)		0/43 (0%)		0/23 (0%)		0/2 (0%)
Nail disorder	2/87 (2.3%)		3/43 (7%)		0/23 (0%)		0/2 (0%)
Vascular disorders
Hypertension	30/87 (34.5%)		8/43 (18.6%)		2/23 (8.7%)		0/2 (0%)
Hypotension	9/87 (10.3%)		0/43 (0%)		0/23 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.