Neoplasms, Breast
Conditions
Keywords
breast cancer
Brief summary
The purpose of this research study is to find how breast cancer responds to the investigational drug, Ispinesib. An investigational drug is a drug that has not been approved by the Food and Drug Administration (FDA) and is available for research use only. In particular, this study will try is to find the answers to the following research questions: 1. Does breast cancer respond to Ispinesib? 2. What are the side effects of Ispinesib? 3. How much Ispinesib is in the blood at specific times after it is taken?
Interventions
DRUGIspinesib
Given intravenously at a dose of 18 milligram (mg)/ meter square (m\^2).
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage IIIB or Stage IV breast cancer * Previously received anthracycline and taxane therapy
Exclusion criteria
* Actively receiving anti-cancer therapy agent(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response Rate (ORR) Following Administration of Ispinesib | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | Overall tumor response rate, was defined as the percentage of participants achieving either a complete response (CR) or partial response (PR), stable disease (SD), or progressive disease (PD). It was assessed by Computer tomography (CT) or Magnetic Resonance Imaging (MRI) scan. Response and progression was evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The target lesions (TLs): CR, Disappearance of all TLs; PR where at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD; PD : At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | For the participants who had a CR or PR, duration of response was defined as the time a CR or PR was first documented, until the first documented sign of disease progression or death. CR for TLs was defined as disappearance of all TLs and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD. The PD defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For participants who did not progress or die, duration of response would be censored at the time of initiation of alternative anti-cancer therapy or time of last contact, if sooner. Due to small number of participants with a response, data was not summarized; however, individual participants data is reported week wise. |
| Median Time-to-progression After Administration of Inspinesib | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | Time-to-progression was defined as the time from the start of treatment until the first documented sign of disease progression or death due to any cause, if sooner. The PD as per RECIST criteria 1.0 was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For participants who did not progress or die, time-to-progression was censored at the time of initiation of alternative anti-cancer therapy or time of last contact, if sooner. |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | From first dose of study drug (Day 1) to 30 days after the last dose (up to 26 months) | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. |
| Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | The vital sign examination included temperature, heart rate, SBP and DBP. Participant data for clinical concern vital parameters; SBP (unit: millimeter of Mercury \[mmHg\]: low concern (LC) and high concern (HC) values as 90 and 180 mmHg; DBP: LC and HC values as 40 and 100 mmHg; heart rate (units: beats per minute \[bpm\]): LC and HC as 50 and 140 bpm; and temperature (units: degree celsius): LC and HC as 36 and 41 degree Celsius; outside the mentioned range were reported. The available data for the participants from Cycle 1 (C1) Day 1 (D1); C2D1, C3D1, C4D1, C5D1, post-treatment and any visit post-screening were reported. |
| Median Time to Response | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | Time to response was defined as the time between the start of first dose of the study drug until the first documented evidence of partial or complete tumor response (whichever status was recorded first). When tumor response was confirmed at a repeat assessment, the time to response was taken as the first time the response was observed. For participants who did not show a tumor response, the time was censored at the time of withdrawal from the study for any reason. It was evaluated using RECIST criteria 1.0. CR for TLs was defined as Disappearance of all TLs and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD. |
| Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. A total of 45 to 46 milliliter (ml) of blood over a 21-day cycle of treatment was collected. For clinical chemistry, the parameters assessed were Alanine transaminase (ALT), Aspartate transaminase (AST), Hemoglobin, lymphocytes, neutrophils, platelet count, white blood cell (WBC), albumin, alkaline phosphatase increased, total bilirubin, calcium, creatinine, glucose, potassium and sodium. The toxicities for the clinical chemistry parameters were graded according to the NCI-CTCAE, version 3.0. where; G 0= None (normal limits); G1= Mild, G2=Moderate; G3=Severe; G4= Fatal. The number of participants with toxicity shift grades for clinical chemistry were reported. |
| Pharmacokinetic (PK) Parameter-Clearance | Pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours up to Cycle 10, up to 26 months | The assessment of clearance for SB-715992 was planned to be collected on C1D1 at timepoints; pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours. However, the data for analysis of PK parameter was not collected. |
| PK Parameter-Volume of Distribution | Pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours up to Cycle 10, up to 26 months | The assessment of volume of distribution for SB-715992 was planned to be collected on C1D1 at timepoints; pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours. Additional samples were to be collected in subsequent cycles, only if dose of study drug was adjusted for any reason following Cycle 1. However, the data for analysis of PK parameter was not collected. |
| Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. A total of 45 to 46 milliliter (ml) of blood over a 21-day cycle of treatment was collected. For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, Red blood cell count, white blood cell count (WBC), lymphocytes, monocytes, granulocytes, neutrophils, ,eosinophils and basophils. The toxicities for the hematology parameters were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0. Grade (G) 0= None (normal limits); G1= Mild, G2=Moderate; G3=Severe; G4= Fatal. The toxicity shift grades for Hemoglobin, Lymphocytes, Neutrophils, platelet count and WBC, were reported. |
Countries
Belgium, Malaysia, Singapore, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in females with advanced or metastatic breast cancer. The study was conducted from 30 January 2004 to 25 August 2006, with a total of 50 female participants enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| SB-715992 The eligible participants were administered Ispinesib, intravenously as a one-hour infusion on Day 1 of every 21-day treatment cycle, at a dose of 18 mg/m\^2. The dosing was repeated for up to multiple cycles, until disease progression or removal from treatment due to an unacceptable toxicity or withdrawal of consent. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 1 |
| Overall Study | Disease progression | 45 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | SB-715992 |
|---|---|
| Age, Continuous | 48.7 Years STANDARD_DEVIATION 8.94 |
| Race/Ethnicity, Customized African American/African heritage | 1 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian heritage | 2 Participants |
| Race/Ethnicity, Customized Asian - East Asian heritage | 6 Participants |
| Race/Ethnicity, Customized Asian - South East Asian heritage | 10 Participants |
| Race/Ethnicity, Customized White - Arabic/North African heritage | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European heritage | 30 Participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 50 |
| other Total, other adverse events | 42 / 50 |
| serious Total, serious adverse events | 23 / 50 |
Outcome results
Primary
Percentage of Participants With Overall Response Rate (ORR) Following Administration of Ispinesib
Overall tumor response rate, was defined as the percentage of participants achieving either a complete response (CR) or partial response (PR), stable disease (SD), or progressive disease (PD). It was assessed by Computer tomography (CT) or Magnetic Resonance Imaging (MRI) scan. Response and progression was evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The target lesions (TLs): CR, Disappearance of all TLs; PR where at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD; PD : At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months
Population: Intent to treat population consisted of all participants (n=50) who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB-715992 | Percentage of Participants With Overall Response Rate (ORR) Following Administration of Ispinesib | 8 percentage of participants |
Secondary
Duration of Response
For the participants who had a CR or PR, duration of response was defined as the time a CR or PR was first documented, until the first documented sign of disease progression or death. CR for TLs was defined as disappearance of all TLs and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD. The PD defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For participants who did not progress or die, duration of response would be censored at the time of initiation of alternative anti-cancer therapy or time of last contact, if sooner. Due to small number of participants with a response, data was not summarized; however, individual participants data is reported week wise.
Time frame: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months
Population: ITT population. Only those participants available at that particular timepoints were analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-715992 | Duration of Response | Participant 1 | 6.9 Weeks |
| SB-715992 | Duration of Response | Participant 2 | 9 Weeks |
| SB-715992 | Duration of Response | Participant 3 | 11.7 Weeks |
| SB-715992 | Duration of Response | Participant 4 | 19.1 Weeks |
Secondary
Median Time-to-progression After Administration of Inspinesib
Time-to-progression was defined as the time from the start of treatment until the first documented sign of disease progression or death due to any cause, if sooner. The PD as per RECIST criteria 1.0 was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For participants who did not progress or die, time-to-progression was censored at the time of initiation of alternative anti-cancer therapy or time of last contact, if sooner.
Time frame: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SB-715992 | Median Time-to-progression After Administration of Inspinesib | 5.86 week |
Secondary
Median Time to Response
Time to response was defined as the time between the start of first dose of the study drug until the first documented evidence of partial or complete tumor response (whichever status was recorded first). When tumor response was confirmed at a repeat assessment, the time to response was taken as the first time the response was observed. For participants who did not show a tumor response, the time was censored at the time of withdrawal from the study for any reason. It was evaluated using RECIST criteria 1.0. CR for TLs was defined as Disappearance of all TLs and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD.
Time frame: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SB-715992 | Median Time to Response | 8.07 weeks |
Secondary
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Time frame: From first dose of study drug (Day 1) to 30 days after the last dose (up to 26 months)
Population: ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB-715992 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAEs | 23 Participants |
| SB-715992 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 49 Participants |
| SB-715992 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any deaths | 11 Participants |
Secondary
Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate
The vital sign examination included temperature, heart rate, SBP and DBP. Participant data for clinical concern vital parameters; SBP (unit: millimeter of Mercury \[mmHg\]: low concern (LC) and high concern (HC) values as 90 and 180 mmHg; DBP: LC and HC values as 40 and 100 mmHg; heart rate (units: beats per minute \[bpm\]): LC and HC as 50 and 140 bpm; and temperature (units: degree celsius): LC and HC as 36 and 41 degree Celsius; outside the mentioned range were reported. The available data for the participants from Cycle 1 (C1) Day 1 (D1); C2D1, C3D1, C4D1, C5D1, post-treatment and any visit post-screening were reported.
Time frame: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months
Population: ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | SBP, C1D1, Pre-dose, <CCR | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | SBP, C1D1, post-infusion, missing | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | SBP, C2D1, Missing | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | SBP, C5D1, Missing | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | SBP, post-treatment, Missing | 5 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | SBP, any visit post-screen<CCR | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | DBP, C1D1, pre-dose, >CCR | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | DBP, C1D1, post-infusion, missing | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | DBP, C2D1, missing | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | DBP, C5D1, missing | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | DBP, post-treatment, Missing | 5 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | DBP, post-treatment, >CCR | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | DBP, any visit post-screen, >CCR | 3 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | HR, C1D1, post-infusion, Missing | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | HR, C2D1, Missing | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | HR, post-treament, Missing | 6 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C1D1, pre-dose, Missing | 3 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C1D1, pre-dose, < CCR | 3 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C1D1, post-infusion, Missing | 7 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C1D1, post-infusion, < CCR | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C2D1, Missing | 5 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C2D1, < CCR | 4 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C3D1, Missing | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C3D1, < CCR | 4 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C4D1, Missing | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C4D1, < CCR | 2 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, C5D1, Missing | 1 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, post-treatment, Missing | 5 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, post-treatment, <CCR | 3 Participants |
| SB-715992 | Number of Participants With Clinical Concern Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Temperature and Heart Rate | Temperature, any visit post-screen, Missing | 2 Participants |
Secondary
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts
Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. A total of 45 to 46 milliliter (ml) of blood over a 21-day cycle of treatment was collected. For clinical chemistry, the parameters assessed were Alanine transaminase (ALT), Aspartate transaminase (AST), Hemoglobin, lymphocytes, neutrophils, platelet count, white blood cell (WBC), albumin, alkaline phosphatase increased, total bilirubin, calcium, creatinine, glucose, potassium and sodium. The toxicities for the clinical chemistry parameters were graded according to the NCI-CTCAE, version 3.0. where; G 0= None (normal limits); G1= Mild, G2=Moderate; G3=Severe; G4= Fatal. The number of participants with toxicity shift grades for clinical chemistry were reported.
Time frame: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months
Population: ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | ALT, G0 to G1 | 9 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | ALT, G0 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | ALT, G1 to G0 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | ALT, G1 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | ALT, G1 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | ALT, G2 to G0 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | AST, G0 to G1 | 14 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | AST, G0 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | AST, G1 to G0 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | AST, G1 to G2 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | AST, G1 to G3 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | AST, G2 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Albumin, G0 to G1 | 7 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Albumin, G0 to G2 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Albumin, G1 to G0 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Albumin, G1 to G2 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Alkaline phosphatase, G0 to G1 | 6 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Alkaline phosphatase, G1 to G2 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Alkaline phosphatase, G1 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Alkaline phosphatase, G2 to G1 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Alkaline phosphatase, G2 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Total Bilirubin, G0 to G1 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Total Bilirubin, G0 to G4 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Total Bilirubin, G1 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Calcium, G0 to G1 | 9 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Calcium, G0 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Calcium, G1 to G4 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Creatinine, G0 to G1 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G0 to G1 | 10 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G0 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G0 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G1 to G0 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G1 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G1 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G2 to G1 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G2 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Glucose, G3 to G2 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Potassium, G0 to G1 | 11 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Sodium, G0 to G1 | 6 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Sodium, G0 to G3 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Sodium, G1 to G0 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts | Sodium, G1 to G3 | 1 Participants |
Secondary
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters
Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. A total of 45 to 46 milliliter (ml) of blood over a 21-day cycle of treatment was collected. For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, Red blood cell count, white blood cell count (WBC), lymphocytes, monocytes, granulocytes, neutrophils, ,eosinophils and basophils. The toxicities for the hematology parameters were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0. Grade (G) 0= None (normal limits); G1= Mild, G2=Moderate; G3=Severe; G4= Fatal. The toxicity shift grades for Hemoglobin, Lymphocytes, Neutrophils, platelet count and WBC, were reported.
Time frame: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months
Population: ITT population. Only those participants with data available at the specified time points were analyzed (represented by n=X) in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Hemoglobin, G0 to G1 | 12 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Hemoglobin, G0 to G2 | 4 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Hemoglobin, G1 to G2 | 8 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Hemoglobin, G1 to G4 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Lymphocytes, G0 to G1 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Lymphocytes, G0 to G2 | 4 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Lymphocytes, G0 to G3 | 2 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Lymphocytes, G1 to G2 | 7 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Lymphocytes, G1 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Lymphocytes, G1 to G4 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Lymphocytes, G2 to G3 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Neutrophils, G0 to G1 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Neutrophils, G0 to G2 | 6 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Neutrophils, G0 to G3 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Neutrophils, G0 to G4 | 26 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Neutrophils, G1 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Neutrophils, G1 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Neutrophils, G1 to G4 | 4 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Platelet count, G0 to G1 | 7 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | Platelet count, G0 to G2 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | WBC, G0 to G1 | 7 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | WBC, G0 to G2 | 15 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | WBC, G0 to G3 | 22 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | WBC, G0 to G4 | 3 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | WBC, G1 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | WBC, G2 to G3 | 1 Participants |
| SB-715992 | Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters | WBC, G2 to G4 | 1 Participants |
Secondary
Pharmacokinetic (PK) Parameter-Clearance
The assessment of clearance for SB-715992 was planned to be collected on C1D1 at timepoints; pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours. However, the data for analysis of PK parameter was not collected.
Time frame: Pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours up to Cycle 10, up to 26 months
Population: The data for the outcome 'PK parameter-clearance' was not collected
Secondary
PK Parameter-Volume of Distribution
The assessment of volume of distribution for SB-715992 was planned to be collected on C1D1 at timepoints; pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours. Additional samples were to be collected in subsequent cycles, only if dose of study drug was adjusted for any reason following Cycle 1. However, the data for analysis of PK parameter was not collected.
Time frame: Pre-dose, and post-dose 30 minute to 1 hour, 1.5 to 2.5 hours, 4 to 6 hours and 20 to 24 hours up to Cycle 10, up to 26 months
Population: Data for PK parameter 'Volume of distribution' was not collected.