Novel Epothilone Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment
Conditions:	Breast Cancer Metastases
Interventions:	Drug: Ixabepilone + Capecitabine Drug: Capecitabine

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each 21-day cycle, plus oral capecitabine 1000 mg/m2 twice a day (BID) x 14 days
Capecitabine	Capecitabine 1250 mg/m2 BID x 14 days

Participant Flow: Overall Study

	Ixabepilone + Capecitabine	Capecitabine
STARTED	375	377
Never Treated	5	10
Still on Treatment	0	1
COMPLETED	370^[1]	366^[2]
NOT COMPLETED	5	11
Randomized but Never Treated	5	10
Still on Treatment as of CSR date	0	1

[1]	Participants who are off treatment
[2]	Participants who are off treatment

Baseline Characteristics

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Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each 21-day cycle, plus oral capecitabine 1000 mg/m2 twice a day (BID) x 14 days
Capecitabine	Capecitabine 1250 mg/m2 BID x 14 days

Baseline Measures

	Ixabepilone + Capecitabine	Capecitabine	Total
Number of Participants [units: participants]	375	377	752
Age, Customized [units: participants]
<65 years	336	322	658
>= 65 years	39	54	93
<50 years	135	145	280
>= 50 years	240	231	471
Unknown	0	1	1
Age [units: years] Median ( Full Range )	53.0 ( 25.0 to 76.0 )	52.0 ( 25.0 to 79.0 )	53.0 ( 25.0 to 79.0 )
Gender [units: participants]
Female	375	376	751
Male	0	1	1
Race/Ethnicity, Customized [units: participants]
American Indian or Alaska Native	1	0	1
Asian	83	87	170
Black or African American	11	11	22
White	257	247	504
Other	23	32	55
Disease Sites [units: participants]
Ascites	14	14	28
Bone	168	162	330
Breast	61	63	124
Chest Wall	53	53	106
Effusion	57	55	112
Lymph Node	250	249	499
Other	20	18	38
Peritoneum	7	14	21
Pleura	29	35	64
Skin/Soft Tissue	60	62	122
Visceral, Liver	245	228	473
Visceral, Lung	180	174	354
Visceral, Other	34	28	62
Disease Sites at Baseline [units: participants]
Liver ± Lung ± Skin/Soft Tissue ± Bone	245	228	473
Lung ± Skin/Soft Tissue ± Bone	71	87	158
Skin/Soft Tissue ± Bone	49	52	101
Bone	0	3	3
Other	6	5	11
Karnofsky Performance Status^[1] [units: Units on a scale]
100	108	105	213
90	145	132	277
80	86	102	188
70	33	34	67
<70	0	1	1
Not reported	3	3	6
Menopausal Status [units: participants]
Premenopausal	54	51	105
Perimenopausal	19	23	42
Postmenopausal	288	289	577
Not reported	14	14	28
Number of Disease Sites [units: participants]
1 disease site	39	34	73
2 disease sites	85	98	183
3 disease sites	110	121	231
4 disease sites	79	69	148
≥5 disease sites	58	53	111
Presence of All Lesions [units: participants]
Subjects with at least 1 lesion	371	375	746
Subjects with no lesions	4	2	6
Visceral Disease in Liver and/or Lung [units: participants]
Yes	316	315	631
No	55	60	115
Missing	4	2	6

[1]	Karnofsky Performance Scale Index measures a patient's functional impairment: 100-80=Able to carry on normal activity and work, no special care; 70-50=Unable to work; able to live at home and care for most personal needs with assistance; 40-0=Unable to care for self; institutional or hospital care needed. Score reported in multiples of 10.

Outcome Measures

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1. Primary:

Progression-free Survival (PFS) Per Independent Radiology Review Committee (IRRC) [ based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]

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2. Secondary:

Overall Response Rate (ORR) Per IRRC [ based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]

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3. Secondary:

Duration of Response Per IRRC [ based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]

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4. Secondary:

Time to Response Per IRRC [ based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]

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5. Secondary:

Overall Survival (OS) [ from date of randomization until death ]

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6. Secondary:

Treatment-related Safety Summary [ safety was assessed on a continual basis every cycle while on-treatment and every 4 weeks post treatment until toxicities resolved or were deemed irreversible. ]

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7. Secondary:

Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI) [ Baseline and prior to each 21-day cycle of treatment, and at first posttreatment follow-up assessment. ]

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Measure Type	Secondary
Measure Title	Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI)
Measure Description	Quality of life, as measured by the FBSI, an 8-item, participant-reported instrument to measure symptoms. Each item has 5 possible responses ranging from 0 (not at all) to 4 (very much). The scoring was conducted according to the Functional Assessment of Chronic Illness Therapy manual, Version 4; higher scores reflect fewer symptoms.
Time Frame	Baseline and prior to each 21-day cycle of treatment, and at first posttreatment follow-up assessment.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was conducted on all randomized participants on an intent to treat basis.(Note: while table only reports data up to 24 wks, which represents most results, statistical analysis includes ALL assessments through study and follow-up; a few participants were assessed after more than 100 weeks.)

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each 21-day cycle, plus oral capecitabine 1000 mg/m2 twice a day (BID) x 14 days
Capecitabine	Capecitabine 1250 mg/m2 BID x 14 days

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	375	377
Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI) [units: units on a scale] Mean ( 95% Confidence Interval )
Week 3 (n=282; n=273)	-0.4 ( -0.97 to 0.20 )	0.3 ( -0.28 to 0.84 )
Week 6 (n=227; n=214)	-0.2 ( -0.90 to 0.48 )	1.1 ( 0.30 to 1.83 )
Week 9 (n=194; n=184)	-0.6 ( -1.31 to 0.19 )	1.8 ( 0.97 to 2.58 )
Week 12 (n=173; n=158)	-1.3 ( -2.19 to -0.42 )	1.4 ( 0.55 to 2.18 )
Week 15 (n=148; n=145)	-0.7 ( -1.65 to 0.27 )	1.7 ( 0.73 to 2.72 )
Week 18 (n=122; n=121)	-1.0 ( -2.18 to 0.13 )	1.7 ( 0.76 to 2.63 )
Week 21 (n=116; n=101)	-0.7 ( -1.63 to 0.28 )	1.1 ( 0.01 to 2.21 )
Week 24 (n=95; n=82)	-0.8 ( -1.89 to 0.38 )	2.3 ( 1.13 to 3.41 )

Statistical Analysis 1 for Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI)

Groups ^[1]	All groups
Method ^[2]	Wei-Lachin
P Value ^[3]	.0002

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	There was a statistically significant difference between groups in change from baseline FBSI score favoring capecitabine. A mean change from baseline of 2.5 was considered a clinically meaningful difference (minimally important difference or MID). On-treatment mean changes in the FBSI did not reach the MID in either group.
[2]	Other relevant information, such as adjustments or degrees of freedom:
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[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided

Responsible Party:	Bristol-Myers Squibb ( Study Director )
Study ID Numbers:	CA163-046
Study First Received:	March 26, 2004
Results First Received:	May 1, 2009
Last Updated:	November 16, 2009
ClinicalTrials.gov Identifier:	NCT00080301 History of Changes
Health Authority:	United States: Food and Drug Administration