Study of Ixabepilone in Asian Subjects With Unresectable or Metastatic Gastric Cancer

• Sponsor: R-Pharm (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00983801
• Collaborator: (none)
• Enrollment: 58
• Locations: 9
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study was to determine whether ixabepilone is effective in the treatment of unresectable or metastatic gastric cancer in Asian participants.

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasms	Drug: Ixabepilone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Ixabepilone in Asian Subjects With Unresectable or Metastatic Gastric Cancer Previously Treated With Fluoropyrimidine-based Chemotherapy
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ixabepilone

Drug: Ixabepilone; Vial, Injection, Intravenous (IV), 40 mg/m^2, Every 21 days, Up to 8 cycles or until disease progression or intolerable toxicity. Additional treatment was given in agreement by both the investigator and sponsor. Ixabepilone 40 mg/m^2 was administered as a 3-hour IV infusion on Day 1 of each 21-day (3 week) cycle provided the participant met the retreatment criteria.; Other Names: Ixempra BMS-247550

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Overall Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (RECIST) [During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (maximum time that any participant was on therapy was 30 weeks)]

   Percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) according to modified RECIST, as determined by investigator. CR: Disappearance of all evidence of target and non-target lesions. In case of lymph node, the lesions short axis of all nodes measuring <10 mm. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A 2-sided confidence interval (CI) was computed using Clopper-Pearson method.

Secondary Outcome Measures

1. Time to Response [Assessed every 6 weeks (± 1 week) starting from the first dose of study therapy until CR or PR (up to 12.1 weeks.)]

   Time to response is defined as the time in weeks from the first dose of study therapy until measurement criteria are first met for PR or CR (whichever status is recorded first). CR: Disappearance of all evidence of target and non-target lesions. In case of lymph node lesions, the short axis of all nodes should measure <10 mm. PR: At least 30% reduction from baseline in the sum of the LD of all target lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks of initial assessment.

2. Duration of Response [From the date of first PR or CR assessment to the date of progression, death, or last tumor assessment (maximum: 4.1 months)]

   Defined as the period in months from the time measurement criteria are first met for PR or CR until the first date of documented PD or death. Refer to outcome measure 1 for CR and PR. PD=≥20% increase in the sum of LD of target lesions and an absolute increase of at least 5 mm of tumor size in reference to the smallest sum LD recorded at or following baseline or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. Estimated by Kaplan-Meier product limit method and a 2-sided 95% CI for median duration was computed by Brookmeyer and Crowley method.

3. Progression Free Survival (PFS) [From the date of initiation of study therapy to the date of progression (up to 8.1 months).]

   PFS=the time interval from date of randomization to the earliest (first) progression or date of death. Participants who progressed or died were counted as events. PD=≥20% increase in sum of LD of target lesions and an absolute increase ≥5 mm in tumor size in reference to the smallest sum LD recorded at or following baseline or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. Estimated using the Kaplan-Meier product-limit method for all treated participants and a 2-sided 95% CI for the median PFS was computed by Brookmeyer and Crowley method).

4. Percentage of Participants With Disease Control Rate [During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (maximum time that any participant was on therapy was 30 weeks)]

   Defined as percentage of participants whose best response was PR, CR, or SD as determined by the investigator. SD=Neither PR or PD are met, taking the smallest sum of the LD recorded at baseline as reference. Refer to outcome measure 1 for definition of CR or PR and refer to outcome measure 4 for definition of PD. A 2-sided 95% CI was computed using Clopper-Pearson method.

5. Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 [Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on ixapebilone therapy was 10.5 weeks (range: 3 to 30 weeks)]

   AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade (GR) 3=Severe; and GR4=Life-threatening or disabling. DR=Drug-related. Any Peripheral Neuropathy includes peripheral sensory and motor neuropathies, including muscle weakness, and hypoaesthesia.

6. Number of Participants With Hematology Abnormalities [Assessed once every week for first 3 weeks, as clinically indicated, start of each 3 week cycle (maximum time that any participant was on therapy was 30 weeks).]

   Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=<LLN-3.0*10^9/L; GR2=<3.0-2.0*10^9/L; GR3=<2.0-1.0*10^9/L; GR4=<1.0*10^9/L. Absolute Neutrophil Count (ANC):GR1=<LLN-1.5*10^9 /L; GR2=<1.5-1.0*10^9/L; GR3=<1.0-0.5*10^9/L; GR4=<0.5*10^9/L. Platelets:GR1=<LLN-75.0*10^9/L; GR2=<75.0-50.0*10^9/L; GR3=<50.0-25.0*10^9/L, GR4=<25.0*10^9/L. Hemoglobin:GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL; GR3=<8.0-6.5g/dL, GR4=<6.5g/dL. LLN=lower limit of normal.

7. Number of Participants With Serum Chemistry Abnormalities [Assessed within 2 weeks of first dose and every 3 weeks before therapy dose (maximum time that any participant was on therapy was 30 weeks).]

   Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=>ULN-2.5*ULN; GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4=>20.0*ULN. Total bilirubin: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN. ULN=upper limit of normal.

Other Outcome Measures

1. Number of Participants With Best Response as Assessed With Modified RECIST [During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (to a maximum follow up for tumor response of 30 weeks)]

   Best overall response that any participant can have is the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). PR: At least 30% reduction from baseline in the sum of the LD of all target lesions. PR criteria should be met again after 4 weeks and before 6 weeks. Stable disease (SD)=Neither PR or progressive disease (PD) are met, taking the smallest sum of the LD recorded at baseline as reference. Refer to outcome measure 4 for definition of PD.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed gastric carcinoma originating from the stomach or gastroesophageal junction

• Must have unresectable or metastatic disease

• Asian ethnicity

• Must have failed prior fluoropyrimidine-based chemotherapy

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• measurable disease by with Response Evaluation Criteria in Solid Tumors (RECIST) guidelines

Exclusion Criteria:

• 1 prior chemotherapy regimen in the metastatic setting or >2 prior chemotherapy if subject also received adjuvant therapy

• Receipt of prior ixabepilone

• ECOG ≥2

• Known brain or meningeal metastasis

• Known viral hepatitis

• Prior taxane therapy

• Uncontrolled non-cancer related medical condition

• Second malignancy

• Peripheral neuropathy ≥ grade 2

• Inadequate hematologic, renal and hepatic function

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Hong Kong		Hong Kong	B
2	Local Institution	Nagoya	Aichi	Japan	4648681
3	Local Institution	Sunto-Gun	Shizuoka	Japan	4118777
4	Local Institution	Seoul		Korea, Republic of	135-710
5	Local Institution	Seoul		Korea, Republic of	136-705
6	Local Institution	Seoul		Korea, Republic of	138-736
7	Local Institution	Singapore		Singapore	169610
8	Local Institution	Taipei		Taiwan	112
9	Local Institution	Taoyuan Hsien		Taiwan	333

Sponsors and Collaborators

• R-Pharm

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: R-Pharm
• ClinicalTrials.gov Identifier: NCT00983801
• Other Study ID Numbers: CA163-200
• First Posted: Sep 24, 2009
• Last Update Posted: Oct 28, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Stomach Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	Of 58 participants enrolled in this study, 6 failed screening criteria, and 52 received treatment.

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Period Title: Overall Study
STARTED	52
COMPLETED	52
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Overall Participants	52
Age, Customized (participants) [Number]
< 65 years	40 76.9%
>=65 years	12 23.1%
< 50 years	9 17.3%
>=50 years	43 82.7%
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	56.5
Sex: Female, Male (Count of Participants)
Female	18 34.6%
Male	34 65.4%
Race/Ethnicity, Customized (participants) [Number]
Chinese	23 44.2%
Japanese	15 28.8%
Korean	13 25%
Asian Other	1 1.9%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (participants) [Number]
0 (normal activity)	20 38.5%
1 (symptoms, but fully ambulatory)	32 61.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Overall Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) according to modified RECIST, as determined by investigator. CR: Disappearance of all evidence of target and non-target lesions. In case of lymph node, the lesions short axis of all nodes measuring <10 mm. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A 2-sided confidence interval (CI) was computed using Clopper-Pearson method.
Time Frame	During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (maximum time that any participant was on therapy was 30 weeks)

Outcome Measure Data

Analysis Population Description

Response-evaluable participants: Participants who received at least 1 dose of ixabepilone with measurable disease at baseline and right cancer diagnosis (presence of histologic or cytologic diagnosis of advanced or metastatic adenocarcinoma originating in the stomach or gastroesophageal junction).

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	52
Number (95% Confidence Interval) [percentage of participants]	15.4 29.6%

2. Secondary Outcome

Title	Time to Response
Description	Time to response is defined as the time in weeks from the first dose of study therapy until measurement criteria are first met for PR or CR (whichever status is recorded first). CR: Disappearance of all evidence of target and non-target lesions. In case of lymph node lesions, the short axis of all nodes should measure <10 mm. PR: At least 30% reduction from baseline in the sum of the LD of all target lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks of initial assessment.
Time Frame	Assessed every 6 weeks (± 1 week) starting from the first dose of study therapy until CR or PR (up to 12.1 weeks.)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study therapy and had a response of either CR or PR.

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	8
Median (Full Range) [weeks]	8.9

3. Secondary Outcome

Title	Duration of Response
Description	Defined as the period in months from the time measurement criteria are first met for PR or CR until the first date of documented PD or death. Refer to outcome measure 1 for CR and PR. PD=≥20% increase in the sum of LD of target lesions and an absolute increase of at least 5 mm of tumor size in reference to the smallest sum LD recorded at or following baseline or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. Estimated by Kaplan-Meier product limit method and a 2-sided 95% CI for median duration was computed by Brookmeyer and Crowley method.
Time Frame	From the date of first PR or CR assessment to the date of progression, death, or last tumor assessment (maximum: 4.1 months)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ixabepilone and had either CR or PR. Participants who neither relapsed nor died were censored on the date of their last tumor assessment.

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	8
Median (95% Confidence Interval) [months]	3.1

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS=the time interval from date of randomization to the earliest (first) progression or date of death. Participants who progressed or died were counted as events. PD=≥20% increase in sum of LD of target lesions and an absolute increase ≥5 mm in tumor size in reference to the smallest sum LD recorded at or following baseline or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. Estimated using the Kaplan-Meier product-limit method for all treated participants and a 2-sided 95% CI for the median PFS was computed by Brookmeyer and Crowley method).
Time Frame	From the date of initiation of study therapy to the date of progression (up to 8.1 months).

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ixabepilone. Participants who died without reporting prior progression were considered to have progressed on their death day. Participants who did not progress or die were censored on their last tumor assessment day. Participants without on-study tumor assessments were censored at start date of therapy.

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	52
Median (95% Confidence Interval) [months]	2.8

5. Secondary Outcome

Title	Percentage of Participants With Disease Control Rate
Description	Defined as percentage of participants whose best response was PR, CR, or SD as determined by the investigator. SD=Neither PR or PD are met, taking the smallest sum of the LD recorded at baseline as reference. Refer to outcome measure 1 for definition of CR or PR and refer to outcome measure 4 for definition of PD. A 2-sided 95% CI was computed using Clopper-Pearson method.
Time Frame	During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (maximum time that any participant was on therapy was 30 weeks)

Outcome Measure Data

Analysis Population Description

Response-evaluable participants: Participants who received at least 1 dose of ixabepilone with measurable disease at baseline and right cancer diagnosis (presence of histologic or cytologic diagnosis of advanced or metastatic adenocarcinoma originating in the stomach or gastroesophageal junction).

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	52
Number (95% Confidence Interval) [percentage of participants]	65.4 125.8%

6. Secondary Outcome

Title	Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
Description	AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade (GR) 3=Severe; and GR4=Life-threatening or disabling. DR=Drug-related. Any Peripheral Neuropathy includes peripheral sensory and motor neuropathies, including muscle weakness, and hypoaesthesia.
Time Frame	Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on ixapebilone therapy was 10.5 weeks (range: 3 to 30 weeks)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study therapy.

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	52
Death (due to disease progression)	16 30.8%
Death (due to pneumonia)	1 1.9%
Death within 30 days of last dose of study therapy	4 7.7%
At least one SAE (Any GR)	30 57.7%
At least one SAE (GR 3-4)	21 40.4%
At least one DR SAE (Any GR)	12 23.1%
At least one DR SAE (GR 3-4)	9 17.3%
At least one AE (Any GR)	52 100%
At least one AE (GR 3-4)	41 78.8%
At least one DR AE (Any GR)	50 96.2%
At least one DR AE (GR 3-4)	31 59.6%
AEs leading to study drug discontinuation (Any GR)	10 19.2%
AEs leading to study drug discontinuation (GR 3-4)	7 13.5%
DRAEs leading to study drug discontinuation:Any GR	4 7.7%
DRAEs leading to study drug discontinuation: GR3-4	4 7.7%
Any Peripheral Neuropathy (Any GR)	33 63.5%
Any Peripheral Neuropathy (GR 3-4)	4 7.7%
DR Peripheral Neuropathy (Any GR)	32 61.5%
DR Peripheral Neuropathy (GR 3-4)	4 7.7%

7. Other Pre-specified Outcome

Title	Number of Participants With Best Response as Assessed With Modified RECIST
Description	Best overall response that any participant can have is the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). PR: At least 30% reduction from baseline in the sum of the LD of all target lesions. PR criteria should be met again after 4 weeks and before 6 weeks. Stable disease (SD)=Neither PR or progressive disease (PD) are met, taking the smallest sum of the LD recorded at baseline as reference. Refer to outcome measure 4 for definition of PD.
Time Frame	During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (to a maximum follow up for tumor response of 30 weeks)

Outcome Measure Data

Analysis Population Description

Response-evaluable participants: Participants who received at least 1 dose of ixabepilone with measurable disease at baseline and right cancer diagnosis (presence of histologic or cytologic diagnosis of advanced or metastatic adenocarcinoma originating in the stomach or gastroesophageal junction).

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	52
Partial Response	8 15.4%
Stable Disease	26 50%
Progressive Disease	15 28.8%
Unable to Determine (No tumor assessment)	1 1.9%
Unable to Determine (Other)	2 3.8%

8. Secondary Outcome

Title	Number of Participants With Hematology Abnormalities
Description	Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=<LLN-3.0*10^9/L; GR2=<3.0-2.0*10^9/L; GR3=<2.0-1.0*10^9/L; GR4=<1.0*10^9/L. Absolute Neutrophil Count (ANC):GR1=<LLN-1.5*10^9 /L; GR2=<1.5-1.0*10^9/L; GR3=<1.0-0.5*10^9/L; GR4=<0.5*10^9/L. Platelets:GR1=<LLN-75.0*10^9/L; GR2=<75.0-50.0*10^9/L; GR3=<50.0-25.0*10^9/L, GR4=<25.0*10^9/L. Hemoglobin:GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL; GR3=<8.0-6.5g/dL, GR4=<6.5g/dL. LLN=lower limit of normal.
Time Frame	Assessed once every week for first 3 weeks, as clinically indicated, start of each 3 week cycle (maximum time that any participant was on therapy was 30 weeks).

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ixabepilone and had at least one measurement available during the study therapy period.

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	52
WBC GR1	6 11.5%
WBC GR2	17 32.7%
WBC GR3	20 38.5%
WBC GR4	5 9.6%
ANC GR1	4 7.7%
ANC GR2	7 13.5%
ANC GR3	16 30.8%
ANC GR4	21 40.4%
Platelet Count GR1	18 34.6%
Platelet Count GR2	3 5.8%
Platelet Count GR3	4 7.7%
Platelet Count GR4	0 0%
Hemoglobin GR1	17 32.7%
Hemoglobin GR2	23 44.2%
Hemoglobin GR3	11 21.2%
Hemoglobin GR4	0 0%

9. Secondary Outcome

Title	Number of Participants With Serum Chemistry Abnormalities
Description	Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=>ULN-2.5*ULN; GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4=>20.0*ULN. Total bilirubin: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN. ULN=upper limit of normal.
Time Frame	Assessed within 2 weeks of first dose and every 3 weeks before therapy dose (maximum time that any participant was on therapy was 30 weeks).

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ixabepilone. n=number of participants with at least 1 measurement available during the study therapy period.

Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
Measure Participants	52
ALP GR1 (n=49)	22 42.3%
ALP GR2 (n=49)	1 1.9%
ALP GR3 (n=49)	1 1.9%
ALP GR4 (n=49)	1 1.9%
AST GR1 (n=49)	9 17.3%
AST GR2 (n=49)	0 0%
AST GR3 (n=49)	0 0%
AST GR4 (n=49)	0 0%
ALT GR1 (n=50)	8 15.4%
ALT GR2 (n=50)	1 1.9%
ALT GR3 (n=50)	0 0%
ALT GR4 (n=50)	0 0%
Total bilirubin GR1 (n=49)	0 0%
Total bilirubin GR2 (n=49)	3 5.8%
Total bilirubin GR3 (n=49)	0 0%
Total bilirubin GR4 (n=49)	0 0%
Creatinine GR1 (n=51)	4 7.7%
Creatinine GR2 (n=51)	1 1.9%
Creatinine GR3 (n=51)	0 0%
Creatinine GR4 (n=51)	0 0%

Adverse Events

Time Frame	Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on ixapebilone therapy was 10.5 weeks (range: 3-30 weeks)
Arm/Group Title	Ixabepilone 40 mg/m^2 IV
Arm/Group Description	ixabepilone 40 mg/m^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity.
All Cause Mortality
	Ixabepilone 40 mg/m^2 IV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ixabepilone 40 mg/m^2 IV
	Affected / at Risk (%)	# Events
Total	30/52 (57.7%)
Blood and lymphatic system disorders
NEUTROPENIA	3/52 (5.8%)
FEBRILE NEUTROPENIA	2/52 (3.8%)
Gastrointestinal disorders
ABDOMINAL DISTENSION	1/52 (1.9%)
NAUSEA	2/52 (3.8%)
OBSTRUCTION GASTRIC	1/52 (1.9%)
ILEUS	2/52 (3.8%)
COLONIC OBSTRUCTION	1/52 (1.9%)
MALABSORPTION	1/52 (1.9%)
SMALL INTESTINAL OBSTRUCTION	1/52 (1.9%)
VOMITING	2/52 (3.8%)
ABDOMINAL PAIN	1/52 (1.9%)
General disorders
MUCOSAL INFLAMMATION	1/52 (1.9%)
PYREXIA	3/52 (5.8%)
Infections and infestations
ANAL ABSCESS	1/52 (1.9%)
PNEUMONIA	2/52 (3.8%)
DEVICE RELATED INFECTION	1/52 (1.9%)
NEUTROPENIC SEPSIS	1/52 (1.9%)
Metabolism and nutrition disorders
DECREASED APPETITE	6/52 (11.5%)
HYPONATRAEMIA	1/52 (1.9%)
HYPOPHAGIA	2/52 (3.8%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/52 (1.9%)
MUSCULAR WEAKNESS	1/52 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM MALIGNANT	10/52 (19.2%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL	1/52 (1.9%)
Other (Not Including Serious) Adverse Events
	Ixabepilone 40 mg/m^2 IV
	Affected / at Risk (%)	# Events
Total	51/52 (98.1%)
Blood and lymphatic system disorders
NEUTROPENIA	25/52 (48.1%)
ANAEMIA	6/52 (11.5%)
THROMBOCYTOPENIA	3/52 (5.8%)
LYMPHOPENIA	3/52 (5.8%)
LEUKOPENIA	12/52 (23.1%)
Gastrointestinal disorders
DIARRHOEA	20/52 (38.5%)
ABDOMINAL DISTENSION	4/52 (7.7%)
NAUSEA	15/52 (28.8%)
CONSTIPATION	14/52 (26.9%)
VOMITING	10/52 (19.2%)
ABDOMINAL PAIN	10/52 (19.2%)
STOMATITIS	7/52 (13.5%)
General disorders
CHEST PAIN	3/52 (5.8%)
MUCOSAL INFLAMMATION	3/52 (5.8%)
PYREXIA	8/52 (15.4%)
FATIGUE	24/52 (46.2%)
ASTHENIA	7/52 (13.5%)
Investigations
HAEMOGLOBIN DECREASED	4/52 (7.7%)
WEIGHT DECREASED	11/52 (21.2%)
Metabolism and nutrition disorders
DECREASED APPETITE	33/52 (63.5%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	11/52 (21.2%)
BACK PAIN	7/52 (13.5%)
PAIN IN EXTREMITY	6/52 (11.5%)
MYALGIA	12/52 (23.1%)
Nervous system disorders
HYPOAESTHESIA	6/52 (11.5%)
PERIPHERAL SENSORY NEUROPATHY	26/52 (50%)
HEADACHE	3/52 (5.8%)
DYSGEUSIA	6/52 (11.5%)
DIZZINESS	8/52 (15.4%)
Psychiatric disorders
INSOMNIA	8/52 (15.4%)
Respiratory, thoracic and mediastinal disorders
COUGH	3/52 (5.8%)
Skin and subcutaneous tissue disorders
NAIL DISORDER	6/52 (11.5%)
PRURITUS	9/52 (17.3%)
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	4/52 (7.7%)
ALOPECIA	35/52 (67.3%)
RASH	19/52 (36.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.