IXAMPLE2: A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer

• Sponsor: R-Pharm (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00883116
• Collaborator: (none)
• Enrollment: 551
• Locations: 93
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to investigate whether administration of ixabepilone results in superior outcome as assessed by overall survival compared with that achieved with standard chemotherapy (paclitaxel or doxorubicin) in women with advanced endometrial cancer that has progressed following first-line chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer	Drug: Ixabepilone; Drug: Doxorubicin; Drug: Paclitaxel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 551 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open Label, Randomized, 2 Arm Study of Ixabepilone Administered Every 21 Days Versus Paclitaxel or Doxorubicin Administered Every 21 Days in Women With Advanced Endometrial Cancer Who Have Previously Been Treated With Chemotherapy
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixabepilone, 40 mg/m^2, intravenously (IV) Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Drug: Ixabepilone; Other Names: Ixempra BMS-247550
Active Comparator: Control chemotherapy (Paclitaxel or Doxorubicin) Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.	Drug: Doxorubicin; Other Names: Adriamycin PFS/RDF Adriacin Adriblastina Adriablastine Adrimedac DOXO-CELL Doxolem Doxorubin Farmiblastina Rubex ; Drug: Paclitaxel; Other Names: Taxol Anzatax Asotax Bristaxol Praxel Taxol Konzentrat F1-106

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Date of randomization to date of death or last date censored to up to approximately 26 months]

   Survival was defined as the time from the date of randomization until the date of death. If the patient did not die, OS was censored on the last date he or she was known to be alive.

Secondary Outcome Measures

1. Progression-free Survival [Date of randomization to date of disease progression or death (or date of last tumor assessment for those who did not die or progress) up to approximately 22 months]

   Progression-free survival was defined as the time from randomization to the date of documented disease progression. Patients who died without a reported prior progression were considered to have progressed on the date of their death. Those who did not progress or die were censored on the date of their last tumor assessment. Participants who did not have any on-study tumor assessments were censored on the date they were randomized. Measurable disease was present if the patient had 1 or more measurable lesions.

2. Best Overall Response Rate [Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)]

   Best overall response rate was defined as the number of participants whose best response was either partial response (PR) or complete response (CR) divided by the number of participants in the treatment group. Overall tumor response was based on an integration of the evaluation of target, nontarget, and new lesions. CR=Disappearance of all clinical and radiologic evidence of target lesions. PR=At least 30% reduction in the sum of diameters of all target lesions; taking as reference the baseline study measurement. Changes in tumor measurements need not be confirmed by repeat measurements performed after the criteria for response were first met.

3. Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug [From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days]

   AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related to study drug=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria

• Women aged 18 years and older

• Histologic or cytologic diagnosis of endometrial carcinoma

• Evidence that the cancer is advanced, recurrent, or metastatic and not curable by local measures, such as surgery or radiation.

• Karnofsky performance status >=70

• Measurable or nonmeasurable disease that has progressed since last treatment.

• If only disease is confined to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology.

• Disease in a previously irradiated field is acceptable as the only site of measurable disease only if there has been clear progression since completion of radiotherapy.

• All therapy directed at endometrial cancer must be discontinued 21 days prior to start of treatment, except for hormonal therapy which must be discontinued at least 1 week prior to start of study treatment. Concurrent administration of hormone replacement therapy is allowed.

• Prior therapy: Participants must have failed 1 prior platinum-based chemotherapeutic regimen for endometrial cancer. May have received 2 prior chemotherapy regimens if 1 regimen was given for stage I or II disease. May have received any number of prior non-cytotoxic regimens such as monoclonal antibodies, cytokines, signal transduction inhibitors, or hormonal therapy. Previous radiation therapy is allowed.

Key Exclusion Criteria

• Carcinosarcoma (malignant mixed mullerian tumor)

• Endometrial leiomyosarcoma and endometrial stromal sarcomas

• Participants who received no prior chemotherapy for endometrial cancer or ≥2 prior chemotherapy regimens (exceptions defined in protocol)

• Known brain metastases

• Receipt of prior ixabepilone therapy

• Concurrent active infection requiring antibiotics or other therapy

• Concurrent unstable disease or other debilitating illness, such as congestive heart failure, unstable angina, myocardial infarction, or other cardiac disease that could jeopardize participation, within the last 6 months

• For participants whose prior therapy did not include an anthracycline and therefore may be randomized to doxorubicin, left ventricular ejection fraction <50% as measured by multigated radionuclide angiography or echocardiography

• History of malignancy, except nonmelanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast, within the last 5 years that has not been treated with chemotherapy

• Known human immunodeficiency viral infection

• Psychiatric disorders or other conditions rendering the participant incapable of complying with protocol requirements

• Absolute neutrophil count <1500/mm^3

• Platelets <100,000/mm^3

• Hemoglobin <9 g/dL

• Total bilirubin >1.5*upper limit of normal (ULN), except for those with Gilbert's disease

• Aspartate aminotransferase or alanine aminotransferase >2.5*ULN

• Serum creatinine >1.5*ULN

• Grade ≥2 neuropathy (sensory or motor)

• No concurrent therapy (chemotherapy, hormonal, or investigational) directed at endometrial cancer during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Of South Alabama	Mobile	Alabama	United States	36604
2	Rocky Mountain Gynecologic Oncology	Englewood	Colorado	United States	80113
3	Peter E. Schwartz, Md	New Haven	Connecticut	United States	06510-3206
4	Hematology Oncology, P.C.	Stamford	Connecticut	United States	06902
5	Gynecologic Oncology Assoc.,Inc	Hollywood	Florida	United States	33021
6	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
7	Sarasota Memorial Health Care System	Sarasota	Florida	United States	34239
8	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
9	Georgia Health Science University	Augusta	Georgia	United States	30912-3335
10	Sudarshan K. Sharma, Md	Hinsdale	Illinois	United States	60521
11	Central Dupage Hospital Cancer Center	Warrenville	Illinois	United States	60555
12	St. Vincent Hospital And Health Care Center, Inc.	Indianapolis	Indiana	United States	46260
13	Hematology And Oncology Specialists, Llc	Marrero	Louisiana	United States	70072
14	Women'S Health Specialists	Rockville	Maryland	United States	20852
15	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912
16	University Of Minnesota	Minneapolis	Minnesota	United States	55455-0374
17	Saint Dominic's Gynecologic Oncology	Jackson	Mississippi	United States	39216
18	Matthew A Powell, Md	Saint Louis	Missouri	United States	63110
19	Blumenthal Cancer Center	Charlotte	North Carolina	United States	28204
20	Duke University Medical Center	Durham	North Carolina	United States	27710
21	Peggy And Charles Stephenson Oklahoma Cancer Center	Oklahoma City	Oklahoma	United States	73104
22	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74136
23	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania	United States	19106
24	Magee-Womens Hospital Of Upmc Laboratory	Pittsburgh	Pennsylvania	United States	15213
25	Women & Infants Hospital Of Ri	Providence	Rhode Island	United States	02908
26	Cancer Centers Of The Carolinas	Greenville	South Carolina	United States	29615
27	Tennessee Gynecologic Oncology Group, Llc	Chattanooga	Tennessee	United States	37403
28	University Of Virginia	Charlottesville	Virginia	United States	22908
29	Local Institution	Rosario	Santa Fe	Argentina	S2000DSK
30	Local Institution	La Rioja		Argentina	5300
31	Local Institution	Salta		Argentina	A4406CLA
32	Local Institution	Milton	Queensland	Australia	4064
33	Local Institution	East Bentleigh	Victoria	Australia	3165
34	Local Institution	Gent		Belgium	9000
35	Local Institution	Leuven		Belgium	B-3000
36	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
37	Local Institution	Barretos	Sao Paulo	Brazil	14784-400
38	Local Institution	Jau	Sao Paulo	Brazil	17210-120
39	Local Institution	Sao Paulo		Brazil	01246-000
40	Local Institution	Calgary	Alberta	Canada	T2N 4N2
41	Local Institution	Surrey	British Columbia	Canada	V3V 1Z2
42	Local Institution	Vancouver	British Columbia	Canada	V5Z 4E6
43	Local Institution	Halifax	Nova Scotia	Canada	B3H 1V7
44	Local Institution	Toronto	Ontario	Canada	M5G 2M9
45	Local Institution	Fleurimont	Quebec	Canada	J1H 5N4
46	Local Institution	Montreal	Quebec	Canada	H2L 4M1
47	Local Institution	Brno		Czech Republic	656 53
48	Local Institution	Hradec Kralove		Czech Republic	500 05
49	Local Institution	Copenhagen		Denmark	2100
50	Local Institution	Herlev		Denmark	2730
51	Local Institution	Odense C		Denmark	5000
52	Local Institution	Paris		France	75004
53	Local Institution	Poitiers		France	86000
54	Local Institution	Saint Herblain Cedex		France	44805
55	Local Institution	Villejuif Cedex		France	94800
56	Local Institution	Athens		Greece	11528
57	Local Institution	Budapest		Hungary	1122
58	Local Institution	Miskolc		Hungary	H-3526
59	Local Institution	Brescia		Italy	25123
60	Local Institution	Campobasso		Italy	86100
61	Local Institution	Meldola (fc)		Italy	47014
62	Local Institution	Milano		Italy	20141
63	Local Institution	Monza		Italy	20052
64	Local Institution	Roma		Italy	00168
65	Local Institution	Df	Distrito Federal	Mexico	06720
66	Local Institution	Mexico City	Distrito Federal	Mexico	06726
67	Local Institution	Mexico	Distrito Federal	Mexico	07760
68	Local Institution	Monterrey	Distrito Federal	Mexico	64320
69	Local Institution	Tlalpan	Distrito Federal	Mexico	14080
70	Local Institution	Guadalajara	Jalisco	Mexico	44340
71	Local Institution	Bergen		Norway	5021
72	Local Institution	Oslo		Norway	0310
73	Local Institution	Lima		Peru	34
74	Local Institution	Lima		Peru	Lima 11
75	Local Institution	Lima		Peru	LIMA 13
76	Local Institution	Ivanovo		Russian Federation	153013
77	Local Institution	Moscow		Russian Federation	115 478
78	Local Institution	Moscow		Russian Federation	117997
79	Local Institution	Obninsk		Russian Federation	249036
80	Local Institution	St Pertersburg		Russian Federation	198255
81	Local Institution	St Petersburg		Russian Federation	197758
82	Local Institution	Barcelona		Spain	08035
83	Local Institution	Madrid		Spain	28040
84	Local Institution	Valencia		Spain	46009
85	Local Institution	Goteborg		Sweden	413 45
86	Local Institution	Linkoping		Sweden	581 85
87	Local Institution	Stockholm		Sweden	171 76
88	Local Institution	Umea		Sweden	901 85
89	Local Institution	Uppsala		Sweden	751 85
90	Local Institution	Bristol	Avon	United Kingdom	BS2 8ED
91	Local Institution	Glasgow	Dumfries & Galloway	United Kingdom	G12 0YN
92	Local Institution	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
93	Local Institution	Leeds	Yorkshire	United Kingdom	LS9 7TF

Sponsors and Collaborators

• R-Pharm

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: R-Pharm
• ClinicalTrials.gov Identifier: NCT00883116
• Other Study ID Numbers: CA163-196; 2008-007167-16
• First Posted: Apr 17, 2009
• Last Update Posted: Mar 9, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Endometrial Neoplasms; Paclitaxel; Doxorubicin; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Pre-assignment Detail	551 participants enrolled. 496 randomized (248 ixabepilone, 248 control); 487 received treatment (248 ixabepilone, 239 to control). Reasons not treated include 1 no longer met study criteria, 1 withdrew consent, 1 condition worsened, and 6 non-specified.

Arm/Group Title	Ixabepilone, 40 mg/m^2, IV	Control Chemotherapy
Arm/Group Description	Participants received ixabepilone, 40 mg/m^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression	Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.
Period Title: Overall Study
STARTED	248	248
Received Treatment	248	239
COMPLETED	39	29
NOT COMPLETED	209	219

Baseline Characteristics

Arm/Group Title	Ixabepilone, 40 mg/m^2, IV	Control Chemotherapy	Total
Arm/Group Description	Participants received ixabepilone, 40 mg/m^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression	Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.	Total of all reporting groups
Overall Participants	248	248	496
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	64.0	64.0	64.0
Age, Customized (Number) [Number]
Younger than 65 years	126 50.8%	139 56%	265 53.4%
65 years and older	122 49.2%	109 44%	231 46.6%
Younger than 50 years	14 5.6%	18 7.3%	32 6.5%
50 years and older	234 94.4%	230 92.7%	464 93.5%
Sex: Female, Male (Count of Participants)
Female	248 100%	248 100%	496 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
White	215 86.7%	213 85.9%	428 86.3%
Black or African American	12 4.8%	18 7.3%	30 6%
Asian	6 2.4%	5 2%	11 2.2%
Other	12 4.8%	12 4.8%	24 4.8%
American Indian or Alaska Native	3 1.2%	0 0%	3 0.6%
Karnofsky Performance Scale Index Status (Number) [Number]
100	86 34.7%	86 34.7%	172 34.7%
90	95 38.3%	79 31.9%	174 35.1%
80	48 19.4%	64 25.8%	112 22.6%
70	19 7.7%	16 6.5%	35 7.1%
<70	0 0%	2 0.8%	2 0.4%
Not reported	0 0%	1 0.4%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Survival was defined as the time from the date of randomization until the date of death. If the patient did not die, OS was censored on the last date he or she was known to be alive.
Time Frame	Date of randomization to date of death or last date censored to up to approximately 26 months

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Ixabepilone, 40 mg/m^2, Intravenously (IV)	Control With Chemotherapy (Paclitaxel or Doxorubicin)
Arm/Group Description	Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Participants received paclitaxel, 175 mg/m^2, given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2, given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.
Measure Participants	248	248
Median (95% Confidence Interval) [Months]	10.9	12.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixabepilone, 40 mg/m^2, Intravenously (IV), Control With Chemotherapy (Paclitaxel or Doxorubicin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0397
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 1.0 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival was defined as the time from randomization to the date of documented disease progression. Patients who died without a reported prior progression were considered to have progressed on the date of their death. Those who did not progress or die were censored on the date of their last tumor assessment. Participants who did not have any on-study tumor assessments were censored on the date they were randomized. Measurable disease was present if the patient had 1 or more measurable lesions.
Time Frame	Date of randomization to date of disease progression or death (or date of last tumor assessment for those who did not die or progress) up to approximately 22 months

Outcome Measure Data

Analysis Population Description

All participants with measurable disease at randomization

Arm/Group Title	Ixabepilone, 40 mg/m^2, Intravenously (IV)	Control With Chemotherapy (Paclitaxel or Doxorubicin)
Arm/Group Description	Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.
Measure Participants	223	223
Median (95% Confidence Interval) [Months]	3.4	4.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixabepilone, 40 mg/m^2, Intravenously (IV), Control With Chemotherapy (Paclitaxel or Doxorubicin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8011
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Best Overall Response Rate
Description	Best overall response rate was defined as the number of participants whose best response was either partial response (PR) or complete response (CR) divided by the number of participants in the treatment group. Overall tumor response was based on an integration of the evaluation of target, nontarget, and new lesions. CR=Disappearance of all clinical and radiologic evidence of target lesions. PR=At least 30% reduction in the sum of diameters of all target lesions; taking as reference the baseline study measurement. Changes in tumor measurements need not be confirmed by repeat measurements performed after the criteria for response were first met.
Time Frame	Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)

Outcome Measure Data

Analysis Population Description

All randomized participants with measurable disease

Arm/Group Title	Ixabepilone, 40 mg/m^2, Intravenously (IV)	Control With Chemotherapy (Paclitaxel or Doxorubicin)
Arm/Group Description	Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.
Measure Participants	223	223
Number (95% Confidence Interval) [Percentage of participants]	15.2 6.1%	15.7 6.3%

4. Secondary Outcome

Title	Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related to study drug=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame	From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ixabepilone

Arm/Group Title	Ixabepilone, 40 mg/m^2, Intravenously (IV)	Control With Chemotherapy (Paclitaxel or Doxorubicin)
Arm/Group Description	Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.
Measure Participants	248	239
Any SAEs	89 35.9%	70 28.2%
Any SAE related to study drug	43 17.3%	29 11.7%
Deaths	121 48.8%	95 38.3%
Any AE related to study drug	223 89.9%	215 86.7%
Any AE leading to study drug discontinuation	49 19.8%	37 14.9%
Any peripheral neuropathy AE	108 43.5%	62 25%
Any Grade 3 or higher AE	160 64.5%	148 59.7%

Adverse Events

Time Frame	Day 1 up to 30 days post last dose of study therapy, an average of 4 years
Adverse Event Reporting Description	Study initiated: August 2009; Study Completion: February 2014
Arm/Group Title	Ixabepilone, 40 mg/m^2, Intravenously (IV)		Control With Chemotherapy (Doxorubicin, 60 mg/m^2, IV)		Control With Chemotherapy (Paclitaxel, 175 mg/m^2, IV)
Arm/Group Description	Participants received ixabepilone, 40 mg/m^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression		Participants received doxorubicin, 60 mg/m^2 given intravenously (IV) per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.		Participants received paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity.
All Cause Mortality
	Ixabepilone, 40 mg/m^2, Intravenously (IV)		Control With Chemotherapy (Doxorubicin, 60 mg/m^2, IV)		Control With Chemotherapy (Paclitaxel, 175 mg/m^2, IV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ixabepilone, 40 mg/m^2, Intravenously (IV)		Control With Chemotherapy (Doxorubicin, 60 mg/m^2, IV)		Control With Chemotherapy (Paclitaxel, 175 mg/m^2, IV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	89/248 (35.9%)		59/171 (34.5%)		11/68 (16.2%)
Blood and lymphatic system disorders
Febrile neutropenia	10/248 (4%)		10/171 (5.8%)		1/68 (1.5%)
Leukopenia	3/248 (1.2%)		1/171 (0.6%)		0/68 (0%)
Neutropenia	6/248 (2.4%)		4/171 (2.3%)		0/68 (0%)
Thrombocytopenia	1/248 (0.4%)		1/171 (0.6%)		1/68 (1.5%)
Anaemia	5/248 (2%)		7/171 (4.1%)		1/68 (1.5%)
Pancytopenia	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Cardiac disorders
Myocardial ischaemia	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Pericardial effusion	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Right ventricular failure	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Cardiac tamponade	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Cardio-respiratory arrest	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Atrial fibrillation	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Cardiac failure congestive	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Tachycardia	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Intracardiac thrombus	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Tachyarrhythmia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Endocrine disorders
Hypothyroidism	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Gastrointestinal disorders
Dyspepsia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Rectal obstruction	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Small intestinal obstruction	1/248 (0.4%)		2/171 (1.2%)		1/68 (1.5%)
Upper gastrointestinal haemorrhage	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Ascites	3/248 (1.2%)		1/171 (0.6%)		0/68 (0%)
Intestinal obstruction	1/248 (0.4%)		3/171 (1.8%)		0/68 (0%)
Oesophagitis	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Gastrointestinal obstruction	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Rectal haemorrhage	1/248 (0.4%)		2/171 (1.2%)		0/68 (0%)
Dysphagia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Nausea	8/248 (3.2%)		7/171 (4.1%)		0/68 (0%)
Abdominal pain	4/248 (1.6%)		6/171 (3.5%)		2/68 (2.9%)
Haematemesis	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Ileus	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Large intestinal haemorrhage	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Constipation	4/248 (1.6%)		4/171 (2.3%)		0/68 (0%)
Diarrhoea	9/248 (3.6%)		2/171 (1.2%)		1/68 (1.5%)
Stomatitis	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Vomiting	9/248 (3.6%)		4/171 (2.3%)		0/68 (0%)
Abdominal distension	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Enterovesical fistula	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Intestinal perforation	2/248 (0.8%)		2/171 (1.2%)		0/68 (0%)
General disorders
Device malfunction	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Oedema	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Sudden death	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Performance status decreased	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Inflammation	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Pyrexia	4/248 (1.6%)		4/171 (2.3%)		0/68 (0%)
Asthenia	3/248 (1.2%)		0/171 (0%)		0/68 (0%)
Mucosal inflammation	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Pain	1/248 (0.4%)		0/171 (0%)		1/68 (1.5%)
General physical health deterioration	1/248 (0.4%)		0/171 (0%)		1/68 (1.5%)
Death	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Fatigue	4/248 (1.6%)		1/171 (0.6%)		0/68 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Cholecystitis	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Infections and infestations
Endocarditis	1/248 (0.4%)		0/171 (0%)		1/68 (1.5%)
Pyelonephritis	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Neutropenic sepsis	0/248 (0%)		2/171 (1.2%)		0/68 (0%)
Pneumonia	0/248 (0%)		3/171 (1.8%)		0/68 (0%)
Pyelonephritis chronic	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Cellulitis	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Clostridium bacteraemia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Device related infection	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Localised infection	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Salmonellosis	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Sepsis	3/248 (1.2%)		2/171 (1.2%)		1/68 (1.5%)
Upper respiratory tract infection	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Infection	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Respiratory moniliasis	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Infectious peritonitis	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Septic shock	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Candidiasis	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Urinary tract infection	4/248 (1.6%)		3/171 (1.8%)		0/68 (0%)
Injury, poisoning and procedural complications
Humerus fracture	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Overdose	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Hip fracture	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Incorrect dose administered	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Investigations
Blood creatinine increased	3/248 (1.2%)		0/171 (0%)		0/68 (0%)
White blood cell count decreased	2/248 (0.8%)		1/171 (0.6%)		0/68 (0%)
Glomerular filtration rate decreased	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Haemoglobin decreased	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
International normalised ratio increased	0/248 (0%)		2/171 (1.2%)		0/68 (0%)
Neutrophil count decreased	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Alanine aminotransferase increased	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Platelet count decreased	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Decreased appetite	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Type 2 diabetes mellitus	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Hypomagnesaemia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Hypoglycaemia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Hyponatraemia	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Dehydration	5/248 (2%)		5/171 (2.9%)		0/68 (0%)
Hypoalbuminaemia	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Hypocalcaemia	0/248 (0%)		1/171 (0.6%)		1/68 (1.5%)
Hypokalaemia	3/248 (1.2%)		0/171 (0%)		0/68 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Arthralgia	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Muscular weakness	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Metastases to central nervous system	1/248 (0.4%)		0/171 (0%)		1/68 (1.5%)
Neoplasm malignant	4/248 (1.6%)		5/171 (2.9%)		0/68 (0%)
Malignant pleural effusion	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Nervous system disorders
Dizziness	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Peripheral motor neuropathy	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Presyncope	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Syncope	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Cerebrovascular accident	2/248 (0.8%)		1/171 (0.6%)		0/68 (0%)
Psychiatric disorders
Anxiety	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Confusional state	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Depression	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Renal and urinary disorders
Haemorrhage urinary tract	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Urinary tract obstruction	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Hydronephrosis	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Renal failure	1/248 (0.4%)		1/171 (0.6%)		0/68 (0%)
Haematuria	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Chromaturia	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Renal failure acute	2/248 (0.8%)		2/171 (1.2%)		1/68 (1.5%)
Ureteric obstruction	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Anuria	2/248 (0.8%)		0/171 (0%)		0/68 (0%)
Urinary bladder haemorrhage	0/248 (0%)		2/171 (1.2%)		0/68 (0%)
Reproductive system and breast disorders
Dyspnoea exertional	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Vaginal haemorrhage	2/248 (0.8%)		1/171 (0.6%)		0/68 (0%)
Female genital tract fistula	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Pulmonary embolism	3/248 (1.2%)		6/171 (3.5%)		0/68 (0%)
Respiratory failure	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Dyspnoea	0/248 (0%)		6/171 (3.5%)		0/68 (0%)
Pneumonia aspiration	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Acute pulmonary oedema	0/248 (0%)		1/171 (0.6%)		0/68 (0%)
Apnoea	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Pulmonary oedema	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Pleural effusion	3/248 (1.2%)		1/171 (0.6%)		1/68 (1.5%)
Skin and subcutaneous tissue disorders
Intertrigo	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Vascular disorders
Embolism	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Orthostatic hypotension	1/248 (0.4%)		0/171 (0%)		0/68 (0%)
Deep vein thrombosis	1/248 (0.4%)		4/171 (2.3%)		0/68 (0%)
Hypertension	0/248 (0%)		0/171 (0%)		1/68 (1.5%)
Other (Not Including Serious) Adverse Events
	Ixabepilone, 40 mg/m^2, Intravenously (IV)		Control With Chemotherapy (Doxorubicin, 60 mg/m^2, IV)		Control With Chemotherapy (Paclitaxel, 175 mg/m^2, IV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	233/248 (94%)		160/171 (93.6%)		63/68 (92.6%)
Blood and lymphatic system disorders
Leukopenia	35/248 (14.1%)		25/171 (14.6%)		6/68 (8.8%)
Neutropenia	58/248 (23.4%)		68/171 (39.8%)		11/68 (16.2%)
Thrombocytopenia	16/248 (6.5%)		12/171 (7%)		2/68 (2.9%)
Anaemia	62/248 (25%)		46/171 (26.9%)		16/68 (23.5%)
Lymphopenia	7/248 (2.8%)		11/171 (6.4%)		0/68 (0%)
Gastrointestinal disorders
Dyspepsia	17/248 (6.9%)		14/171 (8.2%)		0/68 (0%)
Nausea	118/248 (47.6%)		101/171 (59.1%)		17/68 (25%)
Abdominal pain	45/248 (18.1%)		24/171 (14%)		5/68 (7.4%)
Abdominal pain upper	7/248 (2.8%)		14/171 (8.2%)		1/68 (1.5%)
Constipation	77/248 (31%)		49/171 (28.7%)		7/68 (10.3%)
Diarrhoea	76/248 (30.6%)		47/171 (27.5%)		8/68 (11.8%)
Stomatitis	16/248 (6.5%)		18/171 (10.5%)		1/68 (1.5%)
Vomiting	73/248 (29.4%)		48/171 (28.1%)		8/68 (11.8%)
General disorders
Pyrexia	17/248 (6.9%)		22/171 (12.9%)		4/68 (5.9%)
Asthenia	39/248 (15.7%)		24/171 (14%)		11/68 (16.2%)
Mucosal inflammation	21/248 (8.5%)		28/171 (16.4%)		0/68 (0%)
Fatigue	125/248 (50.4%)		88/171 (51.5%)		21/68 (30.9%)
Oedema peripheral	27/248 (10.9%)		20/171 (11.7%)		6/68 (8.8%)
Infections and infestations
Urinary tract infection	22/248 (8.9%)		9/171 (5.3%)		3/68 (4.4%)
Investigations
Haemoglobin decreased	13/248 (5.2%)		11/171 (6.4%)		3/68 (4.4%)
Weight increased	3/248 (1.2%)		2/171 (1.2%)		4/68 (5.9%)
Weight decreased	48/248 (19.4%)		28/171 (16.4%)		3/68 (4.4%)
Metabolism and nutrition disorders
Decreased appetite	82/248 (33.1%)		45/171 (26.3%)		12/68 (17.6%)
Hypomagnesaemia	13/248 (5.2%)		7/171 (4.1%)		0/68 (0%)
Dehydration	14/248 (5.6%)		8/171 (4.7%)		0/68 (0%)
Hypokalaemia	15/248 (6%)		14/171 (8.2%)		2/68 (2.9%)
Musculoskeletal and connective tissue disorders
Pain in extremity	21/248 (8.5%)		12/171 (7%)		8/68 (11.8%)
Arthralgia	46/248 (18.5%)		9/171 (5.3%)		22/68 (32.4%)
Myalgia	32/248 (12.9%)		4/171 (2.3%)		17/68 (25%)
Back pain	21/248 (8.5%)		15/171 (8.8%)		3/68 (4.4%)
Muscular weakness	8/248 (3.2%)		3/171 (1.8%)		4/68 (5.9%)
Nervous system disorders
Dizziness	24/248 (9.7%)		10/171 (5.8%)		1/68 (1.5%)
Hypoaesthesia	3/248 (1.2%)		1/171 (0.6%)		6/68 (8.8%)
Neuropathy peripheral	17/248 (6.9%)		3/171 (1.8%)		5/68 (7.4%)
Dysgeusia	23/248 (9.3%)		18/171 (10.5%)		1/68 (1.5%)
Peripheral motor neuropathy	12/248 (4.8%)		2/171 (1.2%)		5/68 (7.4%)
Peripheral sensory neuropathy	79/248 (31.9%)		10/171 (5.8%)		29/68 (42.6%)
Headache	19/248 (7.7%)		16/171 (9.4%)		0/68 (0%)
Paraesthesia	10/248 (4%)		3/171 (1.8%)		5/68 (7.4%)
Psychiatric disorders
Anxiety	11/248 (4.4%)		13/171 (7.6%)		1/68 (1.5%)
Insomnia	28/248 (11.3%)		13/171 (7.6%)		2/68 (2.9%)
Reproductive system and breast disorders
Vaginal haemorrhage	13/248 (5.2%)		2/171 (1.2%)		4/68 (5.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	37/248 (14.9%)		33/171 (19.3%)		8/68 (11.8%)
Cough	23/248 (9.3%)		16/171 (9.4%)		5/68 (7.4%)
Skin and subcutaneous tissue disorders
Alopecia	102/248 (41.1%)		63/171 (36.8%)		36/68 (52.9%)
Rash	21/248 (8.5%)		7/171 (4.1%)		3/68 (4.4%)

Limitations/Caveats

This study was terminated per Data Monitoring Committee. Results from an interim analysis showed that there was no favorable benefit/risk ratio with ixabepilone and that ixabepilone did not improve survival compared with control chemotherapies.

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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.