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

Sponsor
R-Pharm (Industry)
Overall Status
Completed
CT.gov ID
NCT00080301
Collaborator
(none)
752
Enrollment
127
Locations
2
Arms
54
Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn if BMS-247550 added to the approved therapy of capecitabine is better than capecitabine alone in shrinking or slowing the growth of the cancer in women with metastatic breast cancer who are resistant to taxane and received anthracycline chemotherapy. The safety of this treatment will also be studied.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
752 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Trial of Novel Epothilone BMS-247550 Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With or Resistant to an Anthracycline and Who Are Taxane Resistant
Study Start Date :
Sep 1, 2003
Actual Primary Completion Date :
Nov 1, 2006
Actual Study Completion Date :
Mar 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: A

Drug: Ixabepilone + Capecitabine
Ixabepilone - Intravenous Solution, IV 40mg/m², Day 1 every 21 days, Until progression/unacceptable toxicity Capecitabine (Active Comparator) - Tablet, Oral, 2000 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity
Other Names:
  • BMS-247550
  • IXEMPRA
  • Epothilone

    		•
    Active Comparator: B

    Drug: Capecitabine
    Tablet, Oral, 2500 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity

    Outcome Measures

    Primary Outcome Measures

    1. 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]

      PFS defined as the time in months from randomization to date of progression. Patients who died without a reported prior progression were considered to have progressed on date of death; those who didn't progress or die were censored on date of last tumor assessment. Median PFS time with 95% CI estimated using the Kaplan Meier product limit method.

    Secondary Outcome Measures

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

      Participants with best response of "Complete" or "Partial" according to Response Evaluation Criteria in Solid Tumors (RECIST) a 4-item scale wherein complete response=disappearance of all target lesions and partial response=30% decrease in the sum of the longest diameter of target lesions

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

      Computed for all patients with a best response of "Partial" or "Complete" per RECIST (a 4-item scale as described in previous outcome measure), calculated from the time when these criteria were first met until the first date of documented progression or death.

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

      Time to response was summarized using descriptive statistics and was defined as the time from first dose of study treatment until measurement criteria were first met for Partial Response or Complete Response.

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

      OS was defined as the time from randomization to death. Participants who did not die at the time of the analysis were censored at the latest follow-up date. Median OS with 95% CI was estimated using the Kaplan Meier product limit method.

    5. 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.]

      Laboratory values, adverse events, and other symptoms were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) Version 3.0

    6. 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.]

      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.

    Eligibility Criteria

    Criteria

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

    • Patients must have received either 2 or 3 prior chemotherapy regimens including adjuvant or neoadjuvant therapy.

    • Prior treatment must have included both an anthracycline (i.e., doxorubicin or epirubicin) and a taxane (i.e., paclitaxel or docetaxel).

    • Patients must have received a minimum cumulative dose of anthracycline or must be resistant to an anthracycline.

    • Patients must be resistant to taxane therapy.

    • Patients may not have any history of brain and/or leptomeningeal metastases.

    • Patients may not have CTC Grade 2 or greater neuropathy (motor or sensory).

    • Patients may have not have had prior treatment with an epothilone and/or capecitabine (i.e., Xeloda)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Local Institution Little Rock Arkansas United States
    2 Local Institution San Francisco California United States
    3 Local Institution Vallejo California United States
    4 Local Institution Denver Colorado United States
    5 Local Institution Hartford Connecticut United States
    6 Local Institution Washington District of Columbia United States
    7 Local Institution Orlando Florida United States
    8 Local Institution Baltimore Maryland United States
    9 Local Institution Burlington Massachusetts United States
    10 Local Institution Jackson Mississippi United States
    11 Local Institution Columbia Missouri United States
    12 Local Institution Kansas City Missouri United States
    13 Local Institution Saint Louis Missouri United States
    14 Local Institution Omaha Nebraska United States
    15 Local Institution Livingston New Jersey United States
    16 Local Institution New Brunswick New Jersey United States
    17 Local Institution Albuquerque New Mexico United States
    18 Local Institution New York New York United States
    19 Local Institution Columbus Ohio United States
    20 Local Institution Oklahoma City Oklahoma United States
    21 Local Institution Tulsa Oklahoma United States
    22 Local Institution Pittsburgh Pennsylvania United States
    23 Local Institution Columbia South Carolina United States
    24 Local Institution Greenville South Carolina United States
    25 Local Institution Knoxville Tennessee United States
    26 Local Institution Nashville Tennessee United States
    27 Local Institution Austin Texas United States
    28 Local Institution Houston Texas United States
    29 Local Institution Ogden Utah United States
    30 Local Institution Burlington Vermont United States
    31 Local Institution Tacoma Washington United States
    32 Local Institution Morgantown West Virginia United States
    33 Local Institution Capital Federal Buenos Aires Argentina
    34 Local Institution Haedo Buenos Aires Argentina
    35 Local Institution La Plata Buenos Aires Argentina
    36 Local Institution Mar Del Plata Buenos Aires Argentina
    37 Local Institution Pilar Buenos Aires Argentina
    38 Local Institution Quilmes Buenos Aires Argentina
    39 Local Institution Lanus BuenosAires Argentina
    40 Local Institution Rosario Santa Fe Argentina
    41 Local Institution Cordoba Argentina
    42 Local Institution Neuquen Argentina
    43 Local Institution Santa Fe Argentina
    44 Local Institution Edegem Belgium
    45 Local Institution Gent Belgium
    46 Local Institution Leuven Belgium
    47 Local Institution Liege Belgium
    48 Local Institution Fortaleza Ceara Brazil
    49 Local Institution Belo Horizonte Mina Gerais Brazil
    50 Local Institution Curitiba Parana Brazil
    51 Local Institution Porto Alegre Rio Grande Do Sul Brazil
    52 Local Institution Jau Sao Paulo Brazil
    53 Local Institution Santo Andre Sao Paulo Brazil
    54 Local Institution Sao Paulo - Sp Sao Paulo Brazil
    55 Local Institution Sao Paulo Brazil
    56 Local Institution Vancouver British Columbia Canada
    57 Local Institution Oshawa Ontario Canada
    58 Local Institution Toronto Ontario Canada
    59 Local Institution Montreal Quebec Canada
    60 Local Institution Beijing Beijing China
    61 Local Institution Guangzhou Guangdong China
    62 Local Institution Nanjing Jiangsu China
    63 Local Institution Jinan Shandong China
    64 Local Institution Beijing Shanghai China
    65 Local Institution Xi'An Shanxi China
    66 Local Institution Beijing China
    67 Local Institution Shanghai China
    68 Local Institution Angers France
    69 Local Institution Avignon Cedex 2 France
    70 Local Institution Bayonne France
    71 Local Institution Besancon France
    72 Local Institution Bobigny France
    73 Local Institution Bordeaux France
    74 Local Institution Clermont-Ferrand France
    75 Local Institution Lyon France
    76 Local Institution Nantes France
    77 Local Institution Nice France
    78 Local Institution Saint Brieuc Cedex France
    79 Local Institution Saint-Cloud Cedex France
    80 Local Institution St. Herblain Cedex France
    81 Local Institution Strasbourg Cedex France
    82 Local Institution Toulouse Cedex 3 France
    83 Local Institution Berlin Germany
    84 Local Institution Duisburg Germany
    85 Local Institution Erlangen Germany
    86 Local Institution Athens Greece
    87 Local Institution Thessaloniki Greece
    88 Local Institution Budapest Hungary
    89 Local Institution Debrecen Hungary
    90 Local Institution Gyor Hungary
    91 Local Institution Pecs Hungary
    92 Local Institution Brescia Italy
    93 Local Institution Candiolo (To) Italy
    94 Local Institution Forli Italy
    95 Local Institution San Giovanni Rotondo Italy
    96 Local Institution Incheon Korea, Republic of
    97 Local Institution Seoul Korea, Republic of
    98 Local Institution Nilai Negeri Sembilan Malaysia
    99 Local Institution Kuala Lumpur Malaysia
    100 Local Institution Acapulco Guerrero Mexico
    101 Local Institution Merida Yucatan Mexico
    102 Local Institution Chihuahua Mexico
    103 Local Institution Distrito Federal Mexico
    104 Local Institution San Luis Potosi Mexico
    105 Local Institution Lima Peru
    106 Local Institution Manila Philippines
    107 Local Institution Quezon City Philippines
    108 Local Institution Quezon Philippines
    109 Local Institution Gdansk Poland
    110 Local Institution Opole Poland
    111 Local Institution Barcelona Spain
    112 Local Institution Girona Spain
    113 Local Institution Madrid Spain
    114 Local Institution Valencia Spain
    115 Local Institution Zaragoza Spain
    116 Local Institution Gothenburg Sweden
    117 Local Institution Stockholm Sweden
    118 Local Institution Tainan Taiwan
    119 Local Institution Taipei Taiwan
    120 Local Institution Bangkok Thailand
    121 Local Institution Bristol Avon United Kingdom
    122 Local Institution Chelmsford Essex United Kingdom
    123 Local Institution London Greater London United Kingdom
    124 Local Institution Manchester Greater Manchester United Kingdom
    125 Local Institution Sheffield South Yorkshire United Kingdom
    126 Local Institution Guildford Surrey United Kingdom
    127 Local Institution Newcastle-Upon-Tyne Tyne And Wear United Kingdom

    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:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00080301
    Other Study ID Numbers:
    • CA163-046
    First Posted:
    Mar 30, 2004
    Last Update Posted:
    Nov 2, 2020
    Last Verified:
    Oct 1, 2020
    Keywords provided by , ,
    Metastatic Breast Cancer
    Additional relevant MeSH terms:
    Breast Neoplasms
    Capecitabine
    Epothilones

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description 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 1250 mg/m2 BID x 14 days
    Period Title: Overall Study
    STARTED 375 377
    Never Treated 5 10
    Still on Treatment 0 1
    COMPLETED 370 366
    NOT COMPLETED 5 11

    Baseline Characteristics

    Arm/Group Title Ixabepilone + Capecitabine Capecitabine Total
    Arm/Group Description 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 1250 mg/m2 BID x 14 days Total of all reporting groups
    Overall Participants 375 377 752
    Age, Customized (participants) [Number]
    <65 years
    336
    89.6%
    322
    85.4%
    658
    87.5%
    >= 65 years
    39
    10.4%
    54
    14.3%
    93
    12.4%
    <50 years
    135
    36%
    145
    38.5%
    280
    37.2%
    >= 50 years
    240
    64%
    231
    61.3%
    471
    62.6%
    Unknown
    0
    0%
    1
    0.3%
    1
    0.1%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    53.0
    52.0
    53.0
    Sex: Female, Male (Count of Participants)
    Female
    375
    100%
    376
    99.7%
    751
    99.9%
    Male
    0
    0%
    1
    0.3%
    1
    0.1%
    Race/Ethnicity, Customized (participants) [Number]
    American Indian or Alaska Native
    1
    0.3%
    0
    0%
    1
    0.1%
    Asian
    83
    22.1%
    87
    23.1%
    170
    22.6%
    Black or African American
    11
    2.9%
    11
    2.9%
    22
    2.9%
    White
    257
    68.5%
    247
    65.5%
    504
    67%
    Other
    23
    6.1%
    32
    8.5%
    55
    7.3%
    Disease Sites (participants) [Number]
    Ascites
    14
    3.7%
    14
    3.7%
    28
    3.7%
    Bone
    168
    44.8%
    162
    43%
    330
    43.9%
    Breast
    61
    16.3%
    63
    16.7%
    124
    16.5%
    Chest Wall
    53
    14.1%
    53
    14.1%
    106
    14.1%
    Effusion
    57
    15.2%
    55
    14.6%
    112
    14.9%
    Lymph Node
    250
    66.7%
    249
    66%
    499
    66.4%
    Other
    20
    5.3%
    18
    4.8%
    38
    5.1%
    Peritoneum
    7
    1.9%
    14
    3.7%
    21
    2.8%
    Pleura
    29
    7.7%
    35
    9.3%
    64
    8.5%
    Skin/Soft Tissue
    60
    16%
    62
    16.4%
    122
    16.2%
    Visceral, Liver
    245
    65.3%
    228
    60.5%
    473
    62.9%
    Visceral, Lung
    180
    48%
    174
    46.2%
    354
    47.1%
    Visceral, Other
    34
    9.1%
    28
    7.4%
    62
    8.2%
    Disease Sites at Baseline (participants) [Number]
    Liver ± Lung ± Skin/Soft Tissue ± Bone
    245
    65.3%
    228
    60.5%
    473
    62.9%
    Lung ± Skin/Soft Tissue ± Bone
    71
    18.9%
    87
    23.1%
    158
    21%
    Skin/Soft Tissue ± Bone
    49
    13.1%
    52
    13.8%
    101
    13.4%
    Bone
    0
    0%
    3
    0.8%
    3
    0.4%
    Other
    6
    1.6%
    5
    1.3%
    11
    1.5%
    Karnofsky Performance Status (Units on a scale) [Number]
    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 (participants) [Number]
    Premenopausal
    54
    14.4%
    51
    13.5%
    105
    14%
    Perimenopausal
    19
    5.1%
    23
    6.1%
    42
    5.6%
    Postmenopausal
    288
    76.8%
    289
    76.7%
    577
    76.7%
    Not reported
    14
    3.7%
    14
    3.7%
    28
    3.7%
    Number of Disease Sites (participants) [Number]
    1 disease site
    39
    10.4%
    34
    9%
    73
    9.7%
    2 disease sites
    85
    22.7%
    98
    26%
    183
    24.3%
    3 disease sites
    110
    29.3%
    121
    32.1%
    231
    30.7%
    4 disease sites
    79
    21.1%
    69
    18.3%
    148
    19.7%
    ≥5 disease sites
    58
    15.5%
    53
    14.1%
    111
    14.8%
    Presence of All Lesions (participants) [Number]
    Subjects with at least 1 lesion
    371
    98.9%
    375
    99.5%
    746
    99.2%
    Subjects with no lesions
    4
    1.1%
    2
    0.5%
    6
    0.8%
    Visceral Disease in Liver and/or Lung (participants) [Number]
    Yes
    316
    84.3%
    315
    83.6%
    631
    83.9%
    No
    55
    14.7%
    60
    15.9%
    115
    15.3%
    Missing
    4
    1.1%
    2
    0.5%
    6
    0.8%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS) Per Independent Radiology Review Committee (IRRC)
    Description PFS defined as the time in months from randomization to date of progression. Patients who died without a reported prior progression were considered to have progressed on date of death; those who didn't progress or die were censored on date of last tumor assessment. Median PFS time with 95% CI estimated using the Kaplan Meier product limit method.
    Time Frame based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity

    Outcome Measure Data

    Analysis Population Description
    PFS was analyzed on all randomized patients on an intention to treat basis.
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description 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 1250 mg/m2 BID x 14 days
    Measure Participants 375 377
    Median (95% Confidence Interval) [Months]
    5.85
    4.17
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ixabepilone + Capecitabine, Capecitabine
    Comments Study required 615 events to achieve 90% power to detect a hazard ratio of 0.77 using a 2-sided α = 0.05 log-rank test. The analysis was a comparison between the 2 treatment arms using a 2-sided α=0.0483 log-rank test (adjusted for an interim analysis using the O'Brien Fleming spending function) to reject the null hypothesis of equality of progression free survival. The analysis was conducted when 639 events (310 in combination:329 in capecitabine) were observed from the 752 randomized patients.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value .0003
    Comments Test was stratified by 1) presence of visceral metastases in liver or lung, 2) minimum of either doxorubicin 420 mg/m2 or epirubicin 360 mg/m2, and relapse > 6 months in adjuvant setting, and 3) prior chemotherapy for metastatic disease. (yes/no)
    Method Log Rank
    Comments 95.17% confidence interval is adjusted for the interim analysis.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.75
    Confidence Interval () 95.17%
    0.64 to 0.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Response Rate (ORR) Per IRRC
    Description Participants with best response of "Complete" or "Partial" according to Response Evaluation Criteria in Solid Tumors (RECIST) a 4-item scale wherein complete response=disappearance of all target lesions and partial response=30% decrease in the sum of the longest diameter of target lesions
    Time Frame based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity

    Outcome Measure Data

    Analysis Population Description
    The analysis of ORR was conducted on all randomized patients on an intent to treat basis.
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description 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 1250 mg/m2 BID x 14 days
    Measure Participants 375 377
    Mean (95% Confidence Interval) [percent]
    34.7
    14.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ixabepilone + Capecitabine, Capecitabine
    Comments The study had 95 percent power to detect a significant difference in ORR if the true response rate was 32 percent in the combination arm and 20 percent in the capecitabine arm.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.15
    Confidence Interval () 95%
    2.20 to 4.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Duration of Response Per IRRC
    Description Computed for all patients with a best response of "Partial" or "Complete" per RECIST (a 4-item scale as described in previous outcome measure), calculated from the time when these criteria were first met until the first date of documented progression or death.
    Time Frame based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity

    Outcome Measure Data

    Analysis Population Description
    Results for duration of response apply to only those subjects with a response (defined as complete or partial response).
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description 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 1250 mg/m2 BID x 14 days
    Measure Participants 130 54
    Median (95% Confidence Interval) [months]
    6.4
    5.6
    4. Secondary Outcome
    Title Time to Response Per IRRC
    Description Time to response was summarized using descriptive statistics and was defined as the time from first dose of study treatment until measurement criteria were first met for Partial Response or Complete Response.
    Time Frame based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity

    Outcome Measure Data

    Analysis Population Description
    Results for time to response apply to only those subjects with a response (defined as complete or partial response)
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description 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 1250 mg/m2 BID x 14 days
    Measure Participants 130 54
    Median (Full Range) [weeks]
    11.7
    12.0
    5. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from randomization to death. Participants who did not die at the time of the analysis were censored at the latest follow-up date. Median OS with 95% CI was estimated using the Kaplan Meier product limit method.
    Time Frame from date of randomization until death

    Outcome Measure Data

    Analysis Population Description
    Overall survival was analyzed on all randomized patients on an intent to treat basis.
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description 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 1250 mg/m2 BID x 14 days
    Measure Participants 375 377
    Median (95% Confidence Interval) [Months]
    12.9
    11.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ixabepilone + Capecitabine, Capecitabine
    Comments Study required 631 deaths to achieve 80% power to detect a Hazard ratio of 0.8 using a 2-sided α = 0.05 log rank test. The analysis was a comparison between the 2 treatment arms using a 2-sided α=0.05 log-rank test to reject the null hypothesis of equality of survival. The analysis was conducted when 639 deaths (318 in combination:321 in capecitabine) were observed from the 752 randomized patients.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1936
    Comments Test was stratified by presence of visceral metastases in liver or lung (y/n), minimum of either doxorubicin 420 mg/m2 or epirubicin 360 mg/m2, and relapse > 6 months in adjuvant setting (y/n), and prior chemotherapy for metastatic disease (y/n).
    Method Log Rank
    Comments Test was conducted at the α=0.05 level and no adjustments were performed.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.90
    Confidence Interval () 95.17%
    0.77 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments Confidence Interval adjusted for interim analysis.
    6. Secondary Outcome
    Title Treatment-related Safety Summary
    Description Laboratory values, adverse events, and other symptoms were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) Version 3.0
    Time Frame 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.

    Outcome Measure Data

    Analysis Population Description
    All treated participants; all participants who received at least 1 dose of study therapy.Participants with baseline hepatic impairment (combination arm, n = 29; capecitabine arm, n = 35), defined as Grade ≥2 AST, ALT or Grade ≥1 total bilirubin, were contraindicated due to disproportionate number of toxic deaths.
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest. Capecitabine 1250 mg/m2 BID x 14 days
    Measure Participants 369 368
    Deaths on-study or within 30 days of last dose
    33
    8.8%
    40
    10.6%
    Treatment-related Serious Adverse Events (SAEs)
    91
    24.3%
    31
    8.2%
    Treatment-related Adverse Events (AEs)
    357
    95.2%
    330
    87.5%
    Treatment-related AEs leading to Discontinuation
    137
    36.5%
    25
    6.6%
    7. Secondary Outcome
    Title Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI)
    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.

    Outcome Measure Data

    Analysis Population Description
    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.)
    Arm/Group Title Ixabepilone + Capecitabine Capecitabine
    Arm/Group Description 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 1250 mg/m2 BID x 14 days
    Measure Participants 375 377
    Week 3 (n=282; n=273)
    -0.4
    0.3
    Week 6 (n=227; n=214)
    -0.2
    1.1
    Week 9 (n=194; n=184)
    -0.6
    1.8
    Week 12 (n=173; n=158)
    -1.3
    1.4
    Week 15 (n=148; n=145)
    -0.7
    1.7
    Week 18 (n=122; n=121)
    -1.0
    1.7
    Week 21 (n=116; n=101)
    -0.7
    1.1
    Week 24 (n=95; n=82)
    -0.8
    2.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ixabepilone + Capecitabine, Capecitabine
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value .0002
    Comments
    Method Wei-Lachin
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Capecitabine Ixabepilone + Capecitabine
    Arm/Group Description
    All Cause Mortality
    Capecitabine Ixabepilone + Capecitabine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Capecitabine Ixabepilone + Capecitabine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 127/368 (34.5%) 151/369 (40.9%)
    Blood and lymphatic system disorders
    ANAEMIA 3/368 (0.8%) 11/369 (3%)
    LEUKOPENIA 0/368 (0%) 6/369 (1.6%)
    NEUTROPENIA 0/368 (0%) 18/369 (4.9%)
    COAGULOPATHY 3/368 (0.8%) 0/369 (0%)
    LYMPHADENOPATHY 0/368 (0%) 1/369 (0.3%)
    THROMBOCYTOPENIA 2/368 (0.5%) 7/369 (1.9%)
    BONE MARROW FAILURE 0/368 (0%) 1/369 (0.3%)
    FEBRILE NEUTROPENIA 4/368 (1.1%) 15/369 (4.1%)
    DISSEMINATED INTRAVASCULAR COAGULATION 0/368 (0%) 1/369 (0.3%)
    Cardiac disorders
    ATRIAL FLUTTER 0/368 (0%) 1/369 (0.3%)
    CARDIAC ARREST 0/368 (0%) 1/369 (0.3%)
    CARDIOMYOPATHY 0/368 (0%) 1/369 (0.3%)
    ANGINA PECTORIS 0/368 (0%) 1/369 (0.3%)
    CARDIAC FAILURE 0/368 (0%) 1/369 (0.3%)
    ATRIAL FIBRILLATION 0/368 (0%) 1/369 (0.3%)
    MYOCARDIAL ISCHAEMIA 1/368 (0.3%) 1/369 (0.3%)
    PERICARDIAL EFFUSION 1/368 (0.3%) 0/369 (0%)
    MYOCARDIAL INFARCTION 0/368 (0%) 1/369 (0.3%)
    CARDIOPULMONARY FAILURE 0/368 (0%) 1/369 (0.3%)
    VENTRICULAR DYSFUNCTION 0/368 (0%) 3/369 (0.8%)
    CARDIO-RESPIRATORY ARREST 2/368 (0.5%) 1/369 (0.3%)
    ACUTE MYOCARDIAL INFARCTION 0/368 (0%) 1/369 (0.3%)
    ARRHYTHMIA SUPRAVENTRICULAR 0/368 (0%) 1/369 (0.3%)
    Gastrointestinal disorders
    ILEUS 1/368 (0.3%) 3/369 (0.8%)
    NAUSEA 5/368 (1.4%) 8/369 (2.2%)
    ASCITES 2/368 (0.5%) 1/369 (0.3%)
    COLITIS 1/368 (0.3%) 0/369 (0%)
    MELAENA 1/368 (0.3%) 0/369 (0%)
    VOMITING 8/368 (2.2%) 12/369 (3.3%)
    CHEILITIS 1/368 (0.3%) 0/369 (0%)
    DIARRHOEA 15/368 (4.1%) 14/369 (3.8%)
    DYSPEPSIA 0/368 (0%) 1/369 (0.3%)
    ENTERITIS 2/368 (0.5%) 0/369 (0%)
    GASTRITIS 1/368 (0.3%) 1/369 (0.3%)
    STOMATITIS 1/368 (0.3%) 3/369 (0.8%)
    CONSTIPATION 2/368 (0.5%) 1/369 (0.3%)
    HAEMATEMESIS 1/368 (0.3%) 0/369 (0%)
    OESOPHAGITIS 0/368 (0%) 1/369 (0.3%)
    PANCREATITIS 0/368 (0%) 1/369 (0.3%)
    PEPTIC ULCER 1/368 (0.3%) 0/369 (0%)
    ABDOMINAL PAIN 4/368 (1.1%) 4/369 (1.1%)
    ABDOMINAL PAIN UPPER 1/368 (0.3%) 0/369 (0%)
    EROSIVE OESOPHAGITIS 1/368 (0.3%) 0/369 (0%)
    GASTROINTESTINAL ULCER 0/368 (0%) 1/369 (0.3%)
    GASTROINTESTINAL HAEMORRHAGE 2/368 (0.5%) 0/369 (0%)
    GASTROINTESTINAL OBSTRUCTION 1/368 (0.3%) 0/369 (0%)
    LARGE INTESTINAL OBSTRUCTION 0/368 (0%) 1/369 (0.3%)
    LOWER GASTROINTESTINAL HAEMORRHAGE 0/368 (0%) 2/369 (0.5%)
    General disorders
    PAIN 0/368 (0%) 2/369 (0.5%)
    DEATH 1/368 (0.3%) 2/369 (0.5%)
    CHILLS 0/368 (0%) 1/369 (0.3%)
    FATIGUE 1/368 (0.3%) 3/369 (0.8%)
    PYREXIA 3/368 (0.8%) 9/369 (2.4%)
    ASTHENIA 2/368 (0.5%) 3/369 (0.8%)
    CHEST PAIN 1/368 (0.3%) 1/369 (0.3%)
    SUDDEN DEATH 0/368 (0%) 1/369 (0.3%)
    GENERALISED OEDEMA 1/368 (0.3%) 0/369 (0%)
    MUCOSAL INFLAMMATION 3/368 (0.8%) 4/369 (1.1%)
    PERFORMANCE STATUS DECREASED 0/368 (0%) 1/369 (0.3%)
    GENERAL PHYSICAL HEALTH DETERIORATION 1/368 (0.3%) 1/369 (0.3%)
    Hepatobiliary disorders
    HEPATIC FAILURE 4/368 (1.1%) 1/369 (0.3%)
    ACUTE HEPATIC FAILURE 0/368 (0%) 1/369 (0.3%)
    HEPATOCELLULAR DAMAGE 1/368 (0.3%) 0/369 (0%)
    Immune system disorders
    HYPERSENSITIVITY 0/368 (0%) 2/369 (0.5%)
    TYPE IV HYPERSENSITIVITY REACTION 0/368 (0%) 1/369 (0.3%)
    Infections and infestations
    SEPSIS 0/368 (0%) 5/369 (1.4%)
    MYIASIS 1/368 (0.3%) 0/369 (0%)
    CYSTITIS 0/368 (0%) 1/369 (0.3%)
    INFECTION 2/368 (0.5%) 1/369 (0.3%)
    PNEUMONIA 3/368 (0.8%) 17/369 (4.6%)
    CELLULITIS 0/368 (0%) 3/369 (0.8%)
    ERYSIPELAS 1/368 (0.3%) 1/369 (0.3%)
    LARYNGITIS 0/368 (0%) 1/369 (0.3%)
    PARONYCHIA 0/368 (0%) 1/369 (0.3%)
    BACTERAEMIA 1/368 (0.3%) 0/369 (0%)
    SEPTIC SHOCK 1/368 (0.3%) 1/369 (0.3%)
    HERPES ZOSTER 2/368 (0.5%) 2/369 (0.5%)
    GASTROENTERITIS 1/368 (0.3%) 2/369 (0.5%)
    LOBAR PNEUMONIA 0/368 (0%) 1/369 (0.3%)
    PERITONEAL INFECTION 1/368 (0.3%) 0/369 (0%)
    NEUTROPENIC INFECTION 0/368 (0%) 1/369 (0.3%)
    ENTEROCOLITIS INFECTIOUS 0/368 (0%) 1/369 (0.3%)
    PNEUMONIA STAPHYLOCOCCAL 0/368 (0%) 1/369 (0.3%)
    GASTROINTESTINAL INFECTION 1/368 (0.3%) 0/369 (0%)
    RESPIRATORY TRACT INFECTION 1/368 (0.3%) 2/369 (0.5%)
    GENITOURINARY TRACT INFECTION 1/368 (0.3%) 0/369 (0%)
    LOWER RESPIRATORY TRACT INFECTION 0/368 (0%) 1/369 (0.3%)
    Injury, poisoning and procedural complications
    FALL 0/368 (0%) 2/369 (0.5%)
    OVERDOSE 1/368 (0.3%) 0/369 (0%)
    HIP FRACTURE 1/368 (0.3%) 0/369 (0%)
    ANKLE FRACTURE 1/368 (0.3%) 1/369 (0.3%)
    FEMUR FRACTURE 1/368 (0.3%) 0/369 (0%)
    VASCULAR ACCESS COMPLICATION 0/368 (0%) 1/369 (0.3%)
    POST LUMBAR PUNCTURE SYNDROME 1/368 (0.3%) 0/369 (0%)
    Investigations
    HAEMOGLOBIN DECREASED 1/368 (0.3%) 1/369 (0.3%)
    GRIP STRENGTH DECREASED 0/368 (0%) 1/369 (0.3%)
    PLATELET COUNT DECREASED 2/368 (0.5%) 2/369 (0.5%)
    NEUTROPHIL COUNT DECREASED 0/368 (0%) 1/369 (0.3%)
    GRANULOCYTE COUNT DECREASED 0/368 (0%) 1/369 (0.3%)
    WHITE BLOOD CELL COUNT DECREASED 0/368 (0%) 1/369 (0.3%)
    Metabolism and nutrition disorders
    ANOREXIA 2/368 (0.5%) 2/369 (0.5%)
    DEHYDRATION 3/368 (0.8%) 8/369 (2.2%)
    HYPOKALAEMIA 0/368 (0%) 3/369 (0.8%)
    HYPOVOLAEMIA 0/368 (0%) 1/369 (0.3%)
    HYPOCALCAEMIA 0/368 (0%) 1/369 (0.3%)
    HYPOGLYCAEMIA 1/368 (0.3%) 0/369 (0%)
    HYPONATRAEMIA 0/368 (0%) 3/369 (0.8%)
    HYPERCALCAEMIA 1/368 (0.3%) 1/369 (0.3%)
    HYPERGLYCAEMIA 0/368 (0%) 2/369 (0.5%)
    METABOLIC ACIDOSIS 0/368 (0%) 1/369 (0.3%)
    DIABETIC KETOACIDOSIS 1/368 (0.3%) 0/369 (0%)
    Musculoskeletal and connective tissue disorders
    MYALGIA 0/368 (0%) 3/369 (0.8%)
    TRISMUS 0/368 (0%) 1/369 (0.3%)
    BACK PAIN 1/368 (0.3%) 1/369 (0.3%)
    BONE PAIN 3/368 (0.8%) 1/369 (0.3%)
    ARTHRALGIA 1/368 (0.3%) 1/369 (0.3%)
    MUSCLE SPASMS 0/368 (0%) 1/369 (0.3%)
    PAIN IN EXTREMITY 1/368 (0.3%) 2/369 (0.5%)
    MUSCULOSKELETAL PAIN 1/368 (0.3%) 0/369 (0%)
    PATHOLOGICAL FRACTURE 1/368 (0.3%) 1/369 (0.3%)
    MUSCULOSKELETAL CHEST PAIN 0/368 (0%) 1/369 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CANCER PAIN 1/368 (0.3%) 0/369 (0%)
    BREAST CANCER 1/368 (0.3%) 0/369 (0%)
    METASTATIC PAIN 1/368 (0.3%) 0/369 (0%)
    CERVIX CARCINOMA 1/368 (0.3%) 0/369 (0%)
    INFECTED NEOPLASM 0/368 (0%) 1/369 (0.3%)
    MALIGNANT ASCITES 1/368 (0.3%) 1/369 (0.3%)
    METASTASES TO BONE 0/368 (0%) 1/369 (0.3%)
    NEOPLASM MALIGNANT 1/368 (0.3%) 0/369 (0%)
    METASTASES TO LIVER 2/368 (0.5%) 0/369 (0%)
    METASTASES TO MENINGES 0/368 (0%) 1/369 (0.3%)
    MALIGNANT PLEURAL EFFUSION 2/368 (0.5%) 2/369 (0.5%)
    MALIGNANT NEOPLASM PROGRESSION 36/368 (9.8%) 19/369 (5.1%)
    PERICARDIAL EFFUSION MALIGNANT 4/368 (1.1%) 0/369 (0%)
    METASTASES TO CENTRAL NERVOUS SYSTEM 8/368 (2.2%) 7/369 (1.9%)
    RENAL CELL CARCINOMA STAGE UNSPECIFIED 1/368 (0.3%) 0/369 (0%)
    Nervous system disorders
    APHASIA 1/368 (0.3%) 0/369 (0%)
    SYNCOPE 1/368 (0.3%) 1/369 (0.3%)
    HEADACHE 1/368 (0.3%) 1/369 (0.3%)
    LETHARGY 0/368 (0%) 1/369 (0.3%)
    DIZZINESS 0/368 (0%) 4/369 (1.1%)
    NEURALGIA 0/368 (0%) 1/369 (0.3%)
    CONVULSION 2/368 (0.5%) 0/369 (0%)
    SOMNOLENCE 0/368 (0%) 1/369 (0.3%)
    PARAESTHESIA 0/368 (0%) 1/369 (0.3%)
    HYPOAESTHESIA 0/368 (0%) 1/369 (0.3%)
    MENTAL IMPAIRMENT 0/368 (0%) 1/369 (0.3%)
    CEREBRAL ISCHAEMIA 0/368 (0%) 1/369 (0.3%)
    COGNITIVE DISORDER 1/368 (0.3%) 1/369 (0.3%)
    CEREBRAL HAEMORRHAGE 0/368 (0%) 1/369 (0.3%)
    COORDINATION ABNORMAL 1/368 (0.3%) 1/369 (0.3%)
    INTERCOSTAL NEURALGIA 1/368 (0.3%) 0/369 (0%)
    LOSS OF CONSCIOUSNESS 0/368 (0%) 1/369 (0.3%)
    NEUROPATHY PERIPHERAL 0/368 (0%) 2/369 (0.5%)
    PARESIS CRANIAL NERVE 1/368 (0.3%) 0/369 (0%)
    SPINAL CORD COMPRESSION 1/368 (0.3%) 1/369 (0.3%)
    MARCHIAFAVA-BIGNAMI DISEASE 1/368 (0.3%) 0/369 (0%)
    PERIPHERAL MOTOR NEUROPATHY 1/368 (0.3%) 3/369 (0.8%)
    PERIPHERAL SENSORY NEUROPATHY 0/368 (0%) 5/369 (1.4%)
    Psychiatric disorders
    ANXIETY 1/368 (0.3%) 0/369 (0%)
    DEPRESSION 0/368 (0%) 1/369 (0.3%)
    DISORIENTATION 1/368 (0.3%) 0/369 (0%)
    CONFUSIONAL STATE 2/368 (0.5%) 2/369 (0.5%)
    Renal and urinary disorders
    HAEMATURIA 1/368 (0.3%) 0/369 (0%)
    RENAL FAILURE 1/368 (0.3%) 1/369 (0.3%)
    RENAL IMPAIRMENT 1/368 (0.3%) 0/369 (0%)
    URINARY RETENTION 1/368 (0.3%) 0/369 (0%)
    RENAL FAILURE ACUTE 1/368 (0.3%) 0/369 (0%)
    Reproductive system and breast disorders
    UTERINE HAEMORRHAGE 1/368 (0.3%) 0/369 (0%)
    Respiratory, thoracic and mediastinal disorders
    HYPOXIA 0/368 (0%) 1/369 (0.3%)
    DYSPNOEA 7/368 (1.9%) 14/369 (3.8%)
    DYSPHONIA 0/368 (0%) 1/369 (0.3%)
    HYDROTHORAX 1/368 (0.3%) 0/369 (0%)
    PNEUMONITIS 4/368 (1.1%) 0/369 (0%)
    PNEUMOTHORAX 1/368 (0.3%) 2/369 (0.5%)
    LUNG DISORDER 0/368 (0%) 1/369 (0.3%)
    PLEURITIC PAIN 1/368 (0.3%) 0/369 (0%)
    PLEURAL EFFUSION 9/368 (2.4%) 6/369 (1.6%)
    HYDROPNEUMOTHORAX 1/368 (0.3%) 1/369 (0.3%)
    PULMONARY EMBOLISM 1/368 (0.3%) 2/369 (0.5%)
    RESPIRATORY FAILURE 1/368 (0.3%) 4/369 (1.1%)
    PULMONARY HAEMORRHAGE 1/368 (0.3%) 0/369 (0%)
    ACUTE PULMONARY OEDEMA 0/368 (0%) 1/369 (0.3%)
    PHARYNGOLARYNGEAL PAIN 0/368 (0%) 1/369 (0.3%)
    ACUTE RESPIRATORY DISTRESS SYNDROME 1/368 (0.3%) 0/369 (0%)
    Skin and subcutaneous tissue disorders
    RASH 0/368 (0%) 1/369 (0.3%)
    SKIN ULCER 1/368 (0.3%) 0/369 (0%)
    ERYTHEMA MULTIFORME 0/368 (0%) 1/369 (0.3%)
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME 1/368 (0.3%) 5/369 (1.4%)
    Vascular disorders
    THROMBOSIS 0/368 (0%) 3/369 (0.8%)
    VASCULITIS 0/368 (0%) 1/369 (0.3%)
    HYPOTENSION 2/368 (0.5%) 3/369 (0.8%)
    LYMPHOEDEMA 1/368 (0.3%) 0/369 (0%)
    HYPERTENSION 0/368 (0%) 1/369 (0.3%)
    THROMBOPHLEBITIS 1/368 (0.3%) 0/369 (0%)
    HYPOVOLAEMIC SHOCK 0/368 (0%) 1/369 (0.3%)
    POOR VENOUS ACCESS 1/368 (0.3%) 2/369 (0.5%)
    DEEP VEIN THROMBOSIS 4/368 (1.1%) 0/369 (0%)
    JUGULAR VEIN THROMBOSIS 1/368 (0.3%) 0/369 (0%)
    Other (Not Including Serious) Adverse Events
    Capecitabine Ixabepilone + Capecitabine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 350/368 (95.1%) 360/369 (97.6%)
    Blood and lymphatic system disorders
    ANAEMIA 10/368 (2.7%) 19/369 (5.1%)
    LEUKOPENIA 1/368 (0.3%) 22/369 (6%)
    NEUTROPENIA 9/368 (2.4%) 51/369 (13.8%)
    Eye disorders
    LACRIMATION INCREASED 21/368 (5.7%) 21/369 (5.7%)
    Gastrointestinal disorders
    NAUSEA 164/368 (44.6%) 209/369 (56.6%)
    VOMITING 106/368 (28.8%) 158/369 (42.8%)
    DIARRHOEA 147/368 (39.9%) 179/369 (48.5%)
    DYSPEPSIA 35/368 (9.5%) 34/369 (9.2%)
    STOMATITIS 39/368 (10.6%) 61/369 (16.5%)
    CONSTIPATION 57/368 (15.5%) 120/369 (32.5%)
    ABDOMINAL PAIN 51/368 (13.9%) 68/369 (18.4%)
    ABDOMINAL DISTENSION 12/368 (3.3%) 19/369 (5.1%)
    ABDOMINAL PAIN UPPER 31/368 (8.4%) 45/369 (12.2%)
    General disorders
    PAIN 8/368 (2.2%) 27/369 (7.3%)
    FATIGUE 97/368 (26.4%) 160/369 (43.4%)
    PYREXIA 47/368 (12.8%) 56/369 (15.2%)
    ASTHENIA 57/368 (15.5%) 101/369 (27.4%)
    CHEST PAIN 19/368 (5.2%) 22/369 (6%)
    OEDEMA PERIPHERAL 46/368 (12.5%) 51/369 (13.8%)
    MUCOSAL INFLAMMATION 39/368 (10.6%) 59/369 (16%)
    Infections and infestations
    UPPER RESPIRATORY TRACT INFECTION 16/368 (4.3%) 23/369 (6.2%)
    Investigations
    WEIGHT DECREASED 43/368 (11.7%) 88/369 (23.8%)
    HAEMOGLOBIN DECREASED 4/368 (1.1%) 21/369 (5.7%)
    NEUTROPHIL COUNT DECREASED 6/368 (1.6%) 27/369 (7.3%)
    WHITE BLOOD CELL COUNT DECREASED 3/368 (0.8%) 23/369 (6.2%)
    Metabolism and nutrition disorders
    ANOREXIA 69/368 (18.8%) 127/369 (34.4%)
    DECREASED APPETITE 8/368 (2.2%) 21/369 (5.7%)
    Musculoskeletal and connective tissue disorders
    MYALGIA 24/368 (6.5%) 130/369 (35.2%)
    BACK PAIN 53/368 (14.4%) 46/369 (12.5%)
    BONE PAIN 19/368 (5.2%) 26/369 (7%)
    ARTHRALGIA 25/368 (6.8%) 87/369 (23.6%)
    PAIN IN EXTREMITY 30/368 (8.2%) 70/369 (19%)
    MUSCULOSKELETAL PAIN 16/368 (4.3%) 41/369 (11.1%)
    MUSCULOSKELETAL CHEST PAIN 20/368 (5.4%) 20/369 (5.4%)
    Nervous system disorders
    HEADACHE 41/368 (11.1%) 63/369 (17.1%)
    DIZZINESS 36/368 (9.8%) 48/369 (13%)
    DYSGEUSIA 14/368 (3.8%) 42/369 (11.4%)
    PARAESTHESIA 22/368 (6%) 71/369 (19.2%)
    HYPOAESTHESIA 9/368 (2.4%) 29/369 (7.9%)
    NEUROPATHY PERIPHERAL 5/368 (1.4%) 29/369 (7.9%)
    PERIPHERAL MOTOR NEUROPATHY 8/368 (2.2%) 68/369 (18.4%)
    PERIPHERAL SENSORY NEUROPATHY 30/368 (8.2%) 139/369 (37.7%)
    Psychiatric disorders
    INSOMNIA 25/368 (6.8%) 61/369 (16.5%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 59/368 (16%) 73/369 (19.8%)
    DYSPNOEA 67/368 (18.2%) 61/369 (16.5%)
    Skin and subcutaneous tissue disorders
    RASH 27/368 (7.3%) 45/369 (12.2%)
    ALOPECIA 16/368 (4.3%) 121/369 (32.8%)
    DRY SKIN 25/368 (6.8%) 23/369 (6.2%)
    ERYTHEMA 17/368 (4.6%) 25/369 (6.8%)
    PRURITUS 15/368 (4.1%) 21/369 (5.7%)
    NAIL DISORDER 36/368 (9.8%) 76/369 (20.6%)
    SKIN HYPERPIGMENTATION 53/368 (14.4%) 41/369 (11.1%)
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME 228/368 (62%) 235/369 (63.7%)

    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.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00080301
    Other Study ID Numbers:
    • CA163-046
    First Posted:
    Mar 30, 2004
    Last Update Posted:
    Nov 2, 2020
    Last Verified:
    Oct 1, 2020