Trial Outcomes & Findings for Study Of Ispinesib In Subjects With Breast Cancer (NCT NCT00089973)

Last Updated: 2018-02-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months

Results posted on

2018-02-26

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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 milligram (mg)/ meter square (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.
Overall Study STARTED	50
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	50

Reasons for withdrawal

Reasons for withdrawal
Measure	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 milligram (mg)/ meter square (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.
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	1
Overall Study Disease progression	45
Overall Study Death	1

Baseline Characteristics

Study Of Ispinesib In Subjects With Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SB-715992 n=50 Participants 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.
Age, Continuous	48.7 Years STANDARD_DEVIATION 8.94 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized African American/African heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian heritage	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian heritage	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian heritage	10 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European heritage	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	SB-715992 n=50 Participants 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.
Percentage of Participants With Overall Response Rate (ORR) Following Administration of Ispinesib	8 percentage of participants

SECONDARY outcome

Timeframe: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	SB-715992 n=50 Participants 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.
Median Time to Response	8.07 weeks Interval 5.4 to 10.7

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	SB-715992 n=4 Participants 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.
Duration of Response Participant 1	6.9 Weeks
Duration of Response Participant 2	9 Weeks
Duration of Response Participant 3	11.7 Weeks
Duration of Response Participant 4	19.1 Weeks

SECONDARY outcome

Timeframe: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	SB-715992 n=50 Participants 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.
Median Time-to-progression After Administration of Inspinesib	5.86 week Interval 5.57 to 6.14

SECONDARY outcome

Timeframe: From first dose of study drug (Day 1) to 30 days after the last dose (up to 26 months)

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	SB-715992 n=50 Participants 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.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any SAEs	23 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any AE	49 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any deaths	11 Participants

SECONDARY outcome

Timeframe: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	SB-715992 n=50 Participants 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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	SB-715992 n=50 Participants 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.
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Lymphocytes, G1 to G2	7 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Hemoglobin, G0 to G1	12 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Hemoglobin, G0 to G2	4 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Hemoglobin, G1 to G2	8 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Hemoglobin, G1 to G4	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Lymphocytes, G0 to G1	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Lymphocytes, G0 to G2	4 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Lymphocytes, G0 to G3	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Lymphocytes, G1 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Lymphocytes, G1 to G4	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Lymphocytes, G2 to G3	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Neutrophils, G0 to G1	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Neutrophils, G0 to G2	6 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Neutrophils, G0 to G3	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Neutrophils, G0 to G4	26 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Neutrophils, G1 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Neutrophils, G1 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Neutrophils, G1 to G4	4 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Platelet count, G0 to G1	7 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters Platelet count, G0 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters WBC, G0 to G1	7 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters WBC, G0 to G2	15 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters WBC, G0 to G3	22 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters WBC, G0 to G4	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters WBC, G1 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters WBC, G2 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Hematology Parameters WBC, G2 to G4	1 Participants

SECONDARY outcome

Timeframe: After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	SB-715992 n=50 Participants 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.
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts ALT, G0 to G1	9 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts ALT, G0 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts ALT, G1 to G0	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts ALT, G1 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts ALT, G1 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts ALT, G2 to G0	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts AST, G0 to G1	14 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts AST, G0 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts AST, G1 to G0	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts AST, G1 to G2	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts AST, G1 to G3	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts AST, G2 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Albumin, G0 to G1	7 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Albumin, G0 to G2	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Albumin, G1 to G0	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Albumin, G1 to G2	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Alkaline phosphatase, G0 to G1	6 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Alkaline phosphatase, G1 to G2	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Alkaline phosphatase, G1 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Alkaline phosphatase, G2 to G1	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Alkaline phosphatase, G2 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Total Bilirubin, G0 to G1	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Total Bilirubin, G0 to G4	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Total Bilirubin, G1 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Calcium, G0 to G1	9 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Calcium, G0 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Calcium, G1 to G4	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Creatinine, G0 to G1	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G0 to G1	10 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G0 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G0 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G1 to G0	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G1 to G2	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G1 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G2 to G1	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G2 to G3	1 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Glucose, G3 to G2	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Potassium, G0 to G1	11 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Sodium, G0 to G1	6 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Sodium, G0 to G3	3 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Sodium, G1 to G0	2 Participants
Number of Participants With Toxicity Shift Grade From Baseline for Clinical Chemistry Grade Shifts Sodium, G1 to G3	1 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

SB-715992

Serious events: 23 serious events

Other events: 42 other events

Deaths: 11 deaths

Serious adverse events

Serious adverse events
Measure	SB-715992 n=50 participants at risk 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.
Blood and lymphatic system disorders Febrile neutropenia	10.0% 5/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Blood and lymphatic system disorders Neutropenia	4.0% 2/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Cardiac disorders Pericardial effusion	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Gastrointestinal disorders Vomiting	6.0% 3/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Gastrointestinal disorders Diarrhoea	4.0% 2/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Gastrointestinal disorders Abdominal pain	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Gastrointestinal disorders Ascites	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
General disorders Chest pain	4.0% 2/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
General disorders Pyrexia	4.0% 2/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Hepatobiliary disorders Hyperbilirubinaemia	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Infections and infestations Catheter related infection	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Infections and infestations Neutropenic sepsis	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Nervous system disorders Dizziness	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Nervous system disorders Peripheral motor neuropathy	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Injury, poisoning and procedural complications Spinal compression fracture	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Investigations Hepatic enzyme increased	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Metabolism and nutrition disorders Dehydration	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Musculoskeletal and connective tissue disorders Back pain	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Musculoskeletal and connective tissue disorders Muscle spasms	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Nervous system disorders Hemiparesis	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Nervous system disorders Nervous system disorder	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.0% 2/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.0% 1/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.

Other adverse events

Other adverse events
Measure	SB-715992 n=50 participants at risk 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.
Blood and lymphatic system disorders Neutropenia	40.0% 20/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Gastrointestinal disorders Vomiting	18.0% 9/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Gastrointestinal disorders Diarrhoea	10.0% 5/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Nervous system disorders Dizziness	8.0% 4/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.0% 3/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.
Musculoskeletal and connective tissue disorders Back Pain	6.0% 3/50 • From start of first dose of study drug (D1) to 30 days after the last dose (Up to 26 months) ITT population was used for analysis.

Additional Information

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