Study Of Ispinesib In Subjects With Breast Cancer

Study Overview
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Brief Summary
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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: Does breast cancer respond to Ispinesib? What are the side effects of Ispinesib? How much Ispinesib is in the blood at specific times after it is taken?

Official Title
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Phase II, Open Label Study of Ispinesib in Subjects With Advanced or Metastatic Breast Cancer

Conditions
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Neoplasms, Breast

Intervention / Treatment
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* Drug: Ispinesib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IIIB or Stage IV breast cancer Previously received anthracycline and taxane therapy Exclusion criteria: Actively receiving anti-cancer therapy agent(s).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SB-715992<br>Females with advanced or metastatic breast cancer were administered Ispinesib | Drug: Ispinesib<br>* Given intravenously at a dose of 18 milligram (mg)/ meter square (m^2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | 
| 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. | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | 
| 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. | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | 
| 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. | From first dose of study drug (Day 1) to 30 days after the last dose (up to 26 months) | 
| 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. | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | 
| 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. | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | 
| 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. | After cycle 2 and repeated every 2 cycles up to Cycle 10, up to 26 months | 
| 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. | 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 | 
| 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer