Neoplasms, Gastrointestinal Tract
Conditions
Keywords
c-Met, Metastatic Gastric Carcinoma, adenocarcinoma, Gastric cancer, GSK1363089, XL880, MET inhibitor
Brief summary
This clinical study is being conducted at multiple sites to determine the best confirmed response rate, safety, and tolerability of GSK1363089 treatment in metastatic gastric carcinoma.
Interventions
c-MET tyrosine kinase inhibitor
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* histologically confirmed diagnosis of advanced or metastatic gastric carcinoma, or adenocarcinoma of the gastroesophageal junction or of the distal esophagus. Subjects with tumors of the gastroesophageal junction or of the distal esophagus may be eligible provided that the tumor is not of squamous or sarcomatous histology * Measurable disease * The subject consents to provide paired tumor biopsies, directly prior to commencing study treatment and then between Days 5 and 8. * The subject has an ECOG performance status ≤2. * The subject is able to ingest the GSK1363089 capsules. * In the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level ≥20 μg/dL (552 nmol/L) 30-90 minutes after injection of ACTH. * The subject has liver, kidney and marrow function. * The subject is capable of understanding and complying with the protocol and has signed the informed consent document. * Sexually active subjects (male and female) must use a medically-accepted method of contraception during the course of the study. * Female subjects of childbearing potential must have a negative serum pregnancy test at screening. * The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed ≥5 years ago, and has no evidence of disease for 5 years prior to the screening for this study). * QTc \< 470 msec.
Exclusion criteria
* The subject has received more than two lines of prior cytotoxic chemotherapy for locally advanced or metastatic disease. For the purpose of this protocol, neoadjuvant therapy would not be considered to be prior cytotoxic chemotherapy. In addition, potential subjects who have received prior treatment with c-MET signaling inhibitor are excluded. * The subject has received an investigational drug within 14 days of the first dose of study drug. * The subject has received chemotherapy, immunotherapy, or radiation therapy (to ≥25% of his or her bone marrow) within 14 days or has received nitrosoureas or mitomycin C within 6 weeks prior to the scheduled first dose of GSK1363089. * The subject has AEs due to investigational drugs or other medications administered more than 21 days prior to enrollment that have not recovered to Grade ≤1 using NCI CTCAE v3.0, with the exception of alopecia greater than grade 1. * The subject has known brain metastases. * The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * The subject is pregnant or breastfeeding. * The subject is known to be positive for the human immunodeficiency virus (HIV). * The subject has a previously identified allergy or hypersensitivity to components of the GSK1363089 formulation. * The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response Rate (ORR), of GSK1363089, Per- Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0 | At every 8 Weeks upto 31 months | ORR is defined as the percentage of participants achieving best overall response of confirmed complete response (CR) or partial response (PR). Tumor response for participants with measurable lesions was assessed routinely (after 8 weeks of treatment and approximately every 8 weeks thereafter) using RECIST (version 1.0) criteria. The CR for target lesions was defined as disappearance of all target lesions (TLs) and the non-target lesions (NTLs). PR defined as at least 30% decrease in sum of the longest diameter (LD) of TLs, taking as reference baseline sum LD. The safety population included all participants who passed the screening criteria, enrolled in the study, and received at least 1 dose of study drug. Progressive disease will be used as PD. |
| Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Up to 31 months | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product whether or not it is considered drug related. This would include any side effect, injury, toxicity, sensitivity reaction, abnormal or worsening of a laboratory value, concurrent illness or sudden death. Pre-existing conditions that worsen during a study will be reported as AEs. SAE is an AE that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered SAEs if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. |
| Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years) | Participants systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in mm of mercury (mmHg). These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The data for minimum (min) and maximum (max) post-baseline has been reported. Baseline is defined as the last non-missing record on or before first dose. |
| Change From Baseline in Vital Signs-Pulse Rate | Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years) | The pulse rate or heart rate (HR) for the participant's, were collected after the participant sat quietly for at least five minutes. Baseline evaluations were performed within 72 hours before the first dose. If performed within 24 hours of the first dose, baseline evaluations may serve as the pre-dose Day 1 visit evaluations. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline was defined as pre-dose, Day 1. The HR was measured in beats per minute (bpm). The min and max values have been reported. |
| Change From Baseline in Temperature | Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years) | The body temperature for the participants was assessed. These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline is defined as the last non-missing record on or before first dose. |
| Change From Baseline in Respiratory Rate (RR) | Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years) | The RR for the participant's, were collected after the participant sat quietly for at least five minutes. Baseline evaluations should be performed within 72 hours before the first dose. If performed within 24 hours of the first dose, baseline evaluations may serve as the pre-dose Day 1 visit evaluations. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as pre-dose, Day 1 . The RR was measured in breaths per minute. Min and max post-baseline values are reported. |
| Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | From Day 1 and before 30-day follow- up (up to 2 years) | The data for serum chemistry parameters like albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), amylase, aspartate amino transferase (AST), calcium, carbon dioxide, creatinine, gamma glutamyl transferase (GGT), glucose, blood urea nitrogen (BUN), chloride, free thyroxine, free triiodothyronine, lipase, phosphorous, potassium, sodium, total bilirubin, lactate dehydrogenase, total protein. The abnormal values have been reported wherein data for normal to low and normal to high has been reported. |
| Number of Participants With Shift From Baseline in Serum Chemistry- Graded | From Day 1 to up to 30-day follow-up visit (up to 2 years) | The worst overall common terminology criteria for adverse events version 3.0 (CTCAE) grade (G) shift post baseline for each parameter was mentioned. Only worst case scenarios are presented. CTCAE grading is done as per intensity namely mild moderate severe life-threatening or Death. Analysis was done for Alanine aminotransferases, aspartate aminotransferases, Albumin, alkaline phosphatase, calcium, sodium, potassium, glucose, amylase, amylase, bilirubin, creatinine, phosphate, gamma glutamyl transferases (GGT), and triglycerol lipase. Worst Overall defined as worst post baseline out of normal range flag in the order of (high, low, normal) before 30 day follow up. Data for G3 and G4 is reported. |
| Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | From Day 1 and before 30-day follow- up (up to 2 years) | The hematology parameters worst case overall CTCAE grade shift post Baseline for each parameter was mentioned. CTCAE grading for version 3.0 was used and done as per intensity namely mild moderate severe life-threatening or Death. Participants were analyzed for basophils, eosinophils, erythrocytes, hematocrit, and monocytes were analyzed. Only the abnormal values were reported where normal to high and normal to low changes were reported. Worst Overall was defined as highest post baseline CTCAE grade before 30 day follow up. |
| Number of Participants With Grade Shift for Urinalysis Parameters | From Day 1 and before 30-day follow- up (up to 2 years) | The urinalysis parameters by worst case overall CTCAE grade shift post Baseline for each parameter were mentioned as per the CTCAE grading for version 3.0 and done as per intensity namely mild moderate severe life-threatening or Death. Participants were analyzed for abnormal values for bilirubin, ketones, nitrites, occult blood, pH, protein, specific gravity, and urobilinogen. |
| Number of Participants With Shift From Baseline by Grade for Hematology Parameters | Baseline (pre-dose) and before 30-day follow- up (up to 2 years) | The worst overall grading by CTCAE version 3.0, was used to report the shift from baseline for hematology parameters namely hemoglobin, platelets and lymphocytes. The grades were namely G0, G1, G2, G3 and G4. The data for shifts from G2 to G3 and G0 to G4, mainly the shifts to higher grades G3 and G4 have been reported. |
| Number of Participants Who Required Concomitant Medications | Baseline (pre-dose) and before 30-day follow- up (up to 2 years) | The number of participants who received concomitant medication during the study were reported. The data has been reported for the participants who have received subsequent chemotherapy, subsequent radiation therapy or other therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) of GSK1363089 | At every 8 Weeks upto 31 months | Duration of PFS in months is defined as (Date of Disease Progression/Death - Date of First Dose + 1)/30.44. For participants who did not reach an event (disease progression or death) at the time of data cut-off, duration of PFS is censored at date of last available tumor assessment that is not 'Unable to Evaluate'. For participants who did not have any post-baseline tumor assessments, PFS was censored at Day 1. For any participants who received subsequent anti-cancer therapy, PFS will be right censored at the date of last adequate tumor assessment on or prior to the date of anti-cancer therapy initiation. For any participants who died or progressed after an extended lost-to-follow-up time (greater than 17 weeks), PFS was censored at the date of last adequate assessment prior to extended lost-to follow-up. |
| Duration of Stable Disease of GSK1363089 | At every 8 Weeks upto 31 months | Duration of stable disease, was defined as the time between the date of first dose and death or disease progression, in participants whose best overall response was not progressive disease |
| Disease Stabilization Rate of GSK 1363089 | At every 8 Weeks upto 31 months | It is defined as the number of participants achieving best overall response of confirmed CR or PR or stable disease (SD). It was assessed using RECIST criteria 1.0. The CR for target lesions was defined as disappearance of all TLs and the NTLs. PR is at least 30% decrease in sum of the LD of TLs, taking as reference baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference, the smallest sum LD since the treatment started. |
| Median Duration of Overall Survival (OS)of GSK1363089 | At every 8 Weeks upto 31 months | Duration of OS is defined as (Date of Death \[due to any cause\]) minus Date of first dose. For the participants who were alive at the time of data cut-off, duration of overall survival was censored at the date of last contact. The upper value of the full range was censored observation. |
Countries
United States
Participant flow
Recruitment details
A total of 74 participants with Metastatic gastric cancer were enrolled in this sequential cohort study at 15 sites in the United States of America. The study was conducted from 23 March 2007 to 20 October 2009.
Participants by arm
| Arm | Count |
|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing The eligible participants in this arm were administered GSK1363089 at 240 mg per dosing day orally( viz. foretinib solid capsules of 20, 100 and 200mg) , as 5 days on and 9 days off cycle (no drug for 9-days) every 2 weeks for treatment period of 8 weeks. Participants fasted 2 hours before the dose, followed by a glass of water (after the intake of GSK1363089) and continued to fast 1 hour after each dose. | 48 |
| GSK136308, Daily Dosing The eligible participants in this arm were administered GSK1363089 at 80 mg daily for treatment period of 8 weeks. Participants fasted 2 hours before the dose, followed by a glass of water (after the intake of GSK1363089) and continued to fast 1 hour after each dose. The enrollment in this cohort was started until the enrollment completion in the Intermittent 5 & 9 dosing arm. | 26 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 5 |
| Overall Study | Clinical progression not based on RECIST | 0 | 3 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Hospitalized, unable to continue | 0 | 1 |
| Overall Study | Other: Death | 1 | 0 |
| Overall Study | Progressive disease | 37 | 16 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | GSK136308, Daily Dosing | Total | GSK1363089, Intermittent 5 and 9 Dosing |
|---|---|---|---|
| Age, Continuous | 59.5 Years STANDARD_DEVIATION 15.35 | 59.3 Years STANDARD_DEVIATION 13.57 | 59.1 Years STANDARD_DEVIATION 12.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 60 Participants | 42 Participants |
| Sex: Female, Male Female | 6 Participants | 19 Participants | 13 Participants |
| Sex: Female, Male Male | 20 Participants | 55 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 48 | 0 / 26 |
| other Total, other adverse events | 47 / 48 | 23 / 26 |
| serious Total, serious adverse events | 22 / 48 | 16 / 26 |
Outcome results
Primary
Change From Baseline in Respiratory Rate (RR)
The RR for the participant's, were collected after the participant sat quietly for at least five minutes. Baseline evaluations should be performed within 72 hours before the first dose. If performed within 24 hours of the first dose, baseline evaluations may serve as the pre-dose Day 1 visit evaluations. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as pre-dose, Day 1 . The RR was measured in breaths per minute. Min and max post-baseline values are reported.
Time frame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified time-points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Respiratory Rate (RR) | RR, maximum post baseline | 1.6 breaths per minute | Standard Deviation 2.44 |
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Respiratory Rate (RR) | RR, minimum post baseline | -1.3 breaths per minute | Standard Deviation 1.86 |
| GSK136308, Daily Dosing | Change From Baseline in Respiratory Rate (RR) | RR, maximum post baseline | 1.9 breaths per minute | Standard Deviation 1.89 |
| GSK136308, Daily Dosing | Change From Baseline in Respiratory Rate (RR) | RR, minimum post baseline | -1.3 breaths per minute | Standard Deviation 2.13 |
Primary
Change From Baseline in Temperature
The body temperature for the participants was assessed. These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline is defined as the last non-missing record on or before first dose.
Time frame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Temperature | Temperature, max.post baseline | 0.46 degree celsius | Standard Deviation 0.405 |
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Temperature | Temperature, min.post baseline | -0.48 degree celsius | Standard Deviation 0.626 |
| GSK136308, Daily Dosing | Change From Baseline in Temperature | Temperature, max.post baseline | 2.81 degree celsius | Standard Deviation 12.3 |
| GSK136308, Daily Dosing | Change From Baseline in Temperature | Temperature, min.post baseline | -0.56 degree celsius | Standard Deviation 0.629 |
Primary
Change From Baseline in Vital Signs-Pulse Rate
The pulse rate or heart rate (HR) for the participant's, were collected after the participant sat quietly for at least five minutes. Baseline evaluations were performed within 72 hours before the first dose. If performed within 24 hours of the first dose, baseline evaluations may serve as the pre-dose Day 1 visit evaluations. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline was defined as pre-dose, Day 1. The HR was measured in beats per minute (bpm). The min and max values have been reported.
Time frame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Vital Signs-Pulse Rate | HR, maximum post baseline | 15.4 beats per minute | Standard Deviation 17.16 |
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Vital Signs-Pulse Rate | HR, minimum post baseline | -9.4 beats per minute | Standard Deviation 11 |
| GSK136308, Daily Dosing | Change From Baseline in Vital Signs-Pulse Rate | HR, maximum post baseline | 10.7 beats per minute | Standard Deviation 11.83 |
| GSK136308, Daily Dosing | Change From Baseline in Vital Signs-Pulse Rate | HR, minimum post baseline | -10.8 beats per minute | Standard Deviation 13.17 |
Primary
Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure
Participants systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in mm of mercury (mmHg). These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The data for minimum (min) and maximum (max) post-baseline has been reported. Baseline is defined as the last non-missing record on or before first dose.
Time frame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | SBP, max.post baseline | 25.7 mmHg | Standard Deviation 17.15 |
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | SBP, min.post baseline | -6.3 mmHg | Standard Deviation 18.41 |
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | DBP, max.post baseline | 16.8 mmHg | Standard Deviation 9.21 |
| GSK1363089, Intermittent 5 and 9 Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | DBP, min.post baseline | -3.7 mmHg | Standard Deviation 9.99 |
| GSK136308, Daily Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | DBP, min.post baseline | -3.0 mmHg | Standard Deviation 9.65 |
| GSK136308, Daily Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | SBP, max.post baseline | 23.0 mmHg | Standard Deviation 18.87 |
| GSK136308, Daily Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | DBP, max.post baseline | 15.4 mmHg | Standard Deviation 9.53 |
| GSK136308, Daily Dosing | Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure | SBP, min.post baseline | -5.9 mmHg | Standard Deviation 18.25 |
Primary
Number of Participants Who Required Concomitant Medications
The number of participants who received concomitant medication during the study were reported. The data has been reported for the participants who have received subsequent chemotherapy, subsequent radiation therapy or other therapy.
Time frame: Baseline (pre-dose) and before 30-day follow- up (up to 2 years)
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants Who Required Concomitant Medications | Subsequent Chemotherapy | 22 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants Who Required Concomitant Medications | Subsequent Radiation therapy | 2 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants Who Required Concomitant Medications | Other | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants Who Required Concomitant Medications | Subsequent Chemotherapy | 10 Participants |
| GSK136308, Daily Dosing | Number of Participants Who Required Concomitant Medications | Subsequent Radiation therapy | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants Who Required Concomitant Medications | Other | 1 Participants |
Primary
Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product whether or not it is considered drug related. This would include any side effect, injury, toxicity, sensitivity reaction, abnormal or worsening of a laboratory value, concurrent illness or sudden death. Pre-existing conditions that worsen during a study will be reported as AEs. SAE is an AE that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered SAEs if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.
Time frame: Up to 31 months
Population: Safety population included all participants who passed the screening criteria, enrolled in the study, and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 48 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 22 participants |
| GSK136308, Daily Dosing | Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 26 participants |
| GSK136308, Daily Dosing | Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 16 participants |
Primary
Number of Participants With Grade Shift for Urinalysis Parameters
The urinalysis parameters by worst case overall CTCAE grade shift post Baseline for each parameter were mentioned as per the CTCAE grading for version 3.0 and done as per intensity namely mild moderate severe life-threatening or Death. Participants were analyzed for abnormal values for bilirubin, ketones, nitrites, occult blood, pH, protein, specific gravity, and urobilinogen.
Time frame: From Day 1 and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified timepoints were reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Bilirubin, normal to abnormal | 8 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Ketones, normal to abnormal | 8 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Nitrites, normal to abnormal | 1 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Occult blood, normal to abnormal | 11 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | pH, normal to abnormal | 0 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Protein, normal to abnormal | 13 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Specific gravity, normal to abnormal | 3 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Urobilinogen, normal to abnormal | 3 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Urobilinogen, normal to abnormal | 2 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Bilirubin, normal to abnormal | 3 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | pH, normal to abnormal | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Ketones, normal to abnormal | 11 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Specific gravity, normal to abnormal | 5 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Nitrites, normal to abnormal | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Protein, normal to abnormal | 7 participants |
| GSK136308, Daily Dosing | Number of Participants With Grade Shift for Urinalysis Parameters | Occult blood, normal to abnormal | 9 participants |
Primary
Number of Participants With Objective Response Rate (ORR), of GSK1363089, Per- Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0
ORR is defined as the percentage of participants achieving best overall response of confirmed complete response (CR) or partial response (PR). Tumor response for participants with measurable lesions was assessed routinely (after 8 weeks of treatment and approximately every 8 weeks thereafter) using RECIST (version 1.0) criteria. The CR for target lesions was defined as disappearance of all target lesions (TLs) and the non-target lesions (NTLs). PR defined as at least 30% decrease in sum of the longest diameter (LD) of TLs, taking as reference baseline sum LD. The safety population included all participants who passed the screening criteria, enrolled in the study, and received at least 1 dose of study drug. Progressive disease will be used as PD.
Time frame: At every 8 Weeks upto 31 months
Population: Evaluable population included participants from safety population who had received atleast 75% of protocol mandated doses at treatment period, had BL and post BL tumor assessment, with no extended lost to followup (17 wks or more) or who had received atleast 75% of protocol mandated doses at treatment period and discontinued study drug due to PD.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Objective Response Rate (ORR), of GSK1363089, Per- Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0 | 0 participants |
| GSK136308, Daily Dosing | Number of Participants With Objective Response Rate (ORR), of GSK1363089, Per- Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0 | 0 participants |
Primary
Number of Participants With Shift From Baseline by Grade for Hematology Parameters
The worst overall grading by CTCAE version 3.0, was used to report the shift from baseline for hematology parameters namely hemoglobin, platelets and lymphocytes. The grades were namely G0, G1, G2, G3 and G4. The data for shifts from G2 to G3 and G0 to G4, mainly the shifts to higher grades G3 and G4 have been reported.
Time frame: Baseline (pre-dose) and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by Grade for Hematology Parameters | Hemoglobin, G2 to G3 | 0 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by Grade for Hematology Parameters | Lymphocytes, G2 to G3 | 2 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by Grade for Hematology Parameters | Platelet, G0 to G4 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by Grade for Hematology Parameters | Hemoglobin, G2 to G3 | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by Grade for Hematology Parameters | Lymphocytes, G2 to G3 | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by Grade for Hematology Parameters | Platelet, G0 to G4 | 1 Participants |
Primary
Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters
The hematology parameters worst case overall CTCAE grade shift post Baseline for each parameter was mentioned. CTCAE grading for version 3.0 was used and done as per intensity namely mild moderate severe life-threatening or Death. Participants were analyzed for basophils, eosinophils, erythrocytes, hematocrit, and monocytes were analyzed. Only the abnormal values were reported where normal to high and normal to low changes were reported. Worst Overall was defined as highest post baseline CTCAE grade before 30 day follow up.
Time frame: From Day 1 and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Basophils, Normal to high | 2 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Eosinophils, Normal to low | 2 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Eosinophils, Normal to high | 3 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Erythrocytes, Normal to low | 1 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Erythrocytes, Normal to high | 1 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Erythrocytes, Low to high | 0 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Hematocrit, Normal to low | 3 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Hematocrit, Normal to high | 3 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Monocytes, Normal to low | 5 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Monocytes, Normal to high | 2 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Hematocrit, Normal to high | 0 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Basophils, Normal to high | 0 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Erythrocytes, Low to high | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Eosinophils, Normal to low | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Monocytes, Normal to high | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Eosinophils, Normal to high | 2 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Hematocrit, Normal to low | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Erythrocytes, Normal to low | 2 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Monocytes, Normal to low | 3 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters | Erythrocytes, Normal to high | 2 participants |
Primary
Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded
The data for serum chemistry parameters like albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), amylase, aspartate amino transferase (AST), calcium, carbon dioxide, creatinine, gamma glutamyl transferase (GGT), glucose, blood urea nitrogen (BUN), chloride, free thyroxine, free triiodothyronine, lipase, phosphorous, potassium, sodium, total bilirubin, lactate dehydrogenase, total protein. The abnormal values have been reported wherein data for normal to low and normal to high has been reported.
Time frame: From Day 1 and before 30-day follow- up (up to 2 years)
Population: Safety population. Only those participants available at the specified time points we re analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | BUN, Normal to low | 5 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | BUN, Normal to high | 8 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Chloride, Normal to low | 10 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Chloride, Normal to high | 5 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Thyroxine , Normal to low | NA participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Thyroxine , Normal to high | NA participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Triiodothyronine, Normal to low | NA participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Triiodothyronine, Normal to high | NA participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Triiodothyronine, High to low | NA participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Lactate Dehydrogenase, Normal to high | 28 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Protein, Normal to low | 7 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Protein, Normal to high | 1 participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | TSH, Normal to low | NA participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | TSH, Normal to high | NA participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Protein, Normal to low | 11 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | BUN, Normal to low | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Triiodothyronine, Normal to high | 0 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | BUN, Normal to high | 9 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | TSH, Normal to low | 0 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Chloride, Normal to low | 3 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Triiodothyronine, High to low | 1 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Chloride, Normal to high | 2 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Protein, Normal to high | 0 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Thyroxine , Normal to low | 2 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Lactate Dehydrogenase, Normal to high | 13 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Thyroxine , Normal to high | 0 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | TSH, Normal to high | 7 participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded | Free Triiodothyronine, Normal to low | 1 participants |
Primary
Number of Participants With Shift From Baseline in Serum Chemistry- Graded
The worst overall common terminology criteria for adverse events version 3.0 (CTCAE) grade (G) shift post baseline for each parameter was mentioned. Only worst case scenarios are presented. CTCAE grading is done as per intensity namely mild moderate severe life-threatening or Death. Analysis was done for Alanine aminotransferases, aspartate aminotransferases, Albumin, alkaline phosphatase, calcium, sodium, potassium, glucose, amylase, amylase, bilirubin, creatinine, phosphate, gamma glutamyl transferases (GGT), and triglycerol lipase. Worst Overall defined as worst post baseline out of normal range flag in the order of (high, low, normal) before 30 day follow up. Data for G3 and G4 is reported.
Time frame: From Day 1 to up to 30-day follow-up visit (up to 2 years)
Population: Safety population. Only those participants available at the specified time points were analyzed .
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Alanine aminotransferase, G0 to G3 | 0 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Alanine aminotransferase, G0 to G4 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Albumin, G0 to G3 | 0 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Albumin, G1 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Albumin G2 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Alkaline phosphatase, G0 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Amylase, G0 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Aspartate aminotransferase, G1 to G3 | 4 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Aspartate aminotransferase, G0 to G4 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Aspartate aminotransferase, G2 to G3 | 2 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Bilirubin, G0 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Creatinine, G0 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | GGT, G1 to G3 | 3 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | GGT, G2 to G3 | 2 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Phosphate, G0 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Triacylglycerol Lipase, G0 to G3 | 2 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Triacylglycerol Lipase, G3 to G4 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Sodium, G0 to G3 | 1 Participants |
| GSK1363089, Intermittent 5 and 9 Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Sodium, G1 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Triacylglycerol Lipase, G3 to G4 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Alanine aminotransferase, G0 to G3 | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Aspartate aminotransferase, G2 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Alanine aminotransferase, G0 to G4 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Phosphate, G0 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Albumin, G0 to G3 | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Sodium, G1 to G3 | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Albumin, G1 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Creatinine, G0 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Albumin G2 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Triacylglycerol Lipase, G0 to G3 | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Alkaline phosphatase, G0 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | GGT, G1 to G3 | 1 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Amylase, G0 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Bilirubin, G0 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Sodium, G0 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Aspartate aminotransferase, G1 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | GGT, G2 to G3 | 0 Participants |
| GSK136308, Daily Dosing | Number of Participants With Shift From Baseline in Serum Chemistry- Graded | Aspartate aminotransferase, G0 to G4 | 0 Participants |
Secondary
Disease Stabilization Rate of GSK 1363089
It is defined as the number of participants achieving best overall response of confirmed CR or PR or stable disease (SD). It was assessed using RECIST criteria 1.0. The CR for target lesions was defined as disappearance of all TLs and the NTLs. PR is at least 30% decrease in sum of the LD of TLs, taking as reference baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference, the smallest sum LD since the treatment started.
Time frame: At every 8 Weeks upto 31 months
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Disease Stabilization Rate of GSK 1363089 | 20.8 percentage of participants |
| GSK136308, Daily Dosing | Disease Stabilization Rate of GSK 1363089 | 19.2 percentage of participants |
Secondary
Duration of Stable Disease of GSK1363089
Duration of stable disease, was defined as the time between the date of first dose and death or disease progression, in participants whose best overall response was not progressive disease
Time frame: At every 8 Weeks upto 31 months
Population: Evaluable population. Only those participants available at the specified time-points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Duration of Stable Disease of GSK1363089 | 3.27 months |
| GSK136308, Daily Dosing | Duration of Stable Disease of GSK1363089 | 2.69 months |
Secondary
Median Duration of Overall Survival (OS)of GSK1363089
Duration of OS is defined as (Date of Death \[due to any cause\]) minus Date of first dose. For the participants who were alive at the time of data cut-off, duration of overall survival was censored at the date of last contact. The upper value of the full range was censored observation.
Time frame: At every 8 Weeks upto 31 months
Population: Evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Median Duration of Overall Survival (OS)of GSK1363089 | 7.36 months |
| GSK136308, Daily Dosing | Median Duration of Overall Survival (OS)of GSK1363089 | 4.34 months |
Secondary
Median Progression Free Survival (PFS) of GSK1363089
Duration of PFS in months is defined as (Date of Disease Progression/Death - Date of First Dose + 1)/30.44. For participants who did not reach an event (disease progression or death) at the time of data cut-off, duration of PFS is censored at date of last available tumor assessment that is not 'Unable to Evaluate'. For participants who did not have any post-baseline tumor assessments, PFS was censored at Day 1. For any participants who received subsequent anti-cancer therapy, PFS will be right censored at the date of last adequate tumor assessment on or prior to the date of anti-cancer therapy initiation. For any participants who died or progressed after an extended lost-to-follow-up time (greater than 17 weeks), PFS was censored at the date of last adequate assessment prior to extended lost-to follow-up.
Time frame: At every 8 Weeks upto 31 months
Population: Safety population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK1363089, Intermittent 5 and 9 Dosing | Median Progression Free Survival (PFS) of GSK1363089 | 1.64 months |
| GSK136308, Daily Dosing | Median Progression Free Survival (PFS) of GSK1363089 | 1.77 months |