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Phase II Trial Comparing ABI-007 (Abraxane®, Nab®-Paclitaxel) to Taxotere in First Line Therapy of Patients With Stage IV Breast Cancer

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT00274456
Collaborator
(none)
302
Enrollment
1
Location
4
Arms
67.9
Actual Duration (Months)
4.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was an open-label study conducted comparing the toxicity and antitumor activity of ABI-007 (Abraxane®, nab®-paclitaxel) to docetaxel (Taxotere).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This was an open-label, randomized study to compare the following regimens with respect to toxicity and antitumor activity:

  • the maximum tolerated dose (MTD) of ABI-007 300 mg/m^2 every 3 weeks;

  • ABI-007 100 mg/m^2 administered weekly for 3 weeks with a 1 week rest;

  • ABI-007 150 mg/m^2 administered weekly for 3 weeks with a 1 week rest;

  • the standard dose and schedule of Taxotere (100 mg/m^2 every 3 weeks).

Study Design

Study Type:
Interventional
Actual Enrollment :
302 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Study of Weekly or Every 3 Weeks ABI-007 Versus Every 3 Weeks Taxotere as First Line Therapy of Stage IV (Metastatic) Breast Cancer
Actual Study Start Date :
Nov 1, 2005
Actual Primary Completion Date :
Mar 1, 2008
Actual Study Completion Date :
Jul 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: ABI-007 300 mg/m^2 q3w

ABI-007 300 mg/m^2 administered once every third week (q3w).

Drug: ABI-007
ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment.
Other Names:
  • Abraxane®
  • nab®-paclitaxel

    		•
    Experimental: ABI-007 100 mg/m^2 weekly

    ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest

    Drug: ABI-007
    ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment.
    Other Names:
  • Abraxane®
  • nab®-paclitaxel

    		•
    Experimental: ABI-007 150 mg/m^2 weekly

    ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest

    Drug: ABI-007
    ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment.
    Other Names:
  • Abraxane®
  • nab®-paclitaxel

    		•
    Active Comparator: Docetaxel 100 mg/m^2, q3w

    Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).

    Drug: Docetaxel
    Docetaxel dosed q3w at 100 mg/m^2
    Other Names:
  • Taxotere

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator [Day 1 up to 95 weeks]

      Percentage of participants who achieve an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms. A partial response (PR) is >= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR.

    Secondary Outcome Measures

    1. Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response [Day 1 up to 95 weeks]

      Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately

    2. Kaplan-Meier Estimates for Progression-free Survival (PFS) [Day 1 up to 95 weeks]

      PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

    3. Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression [Day 1 - 95 weeks]

      Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3.

    4. Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression [Day 1 - 95 weeks]

      Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3.

    5. Kaplan-Meier Estimate for Overall Survival (OS) [Day 1 to 221 weeks]

      Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010).

    6. Participants With Treatment-Emergent, Treatment-Related Adverse Events [Day 1 up to 125 weeks]

      Summary of participants who had treatment-emergent that were treatment-related in the opinion of the investigator, and summarized in a variety of categories. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death.

    Other Outcome Measures

    1. Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts [Day 1 up to 125 weeks]

      Maximal degree of myelosuppression is represented by the nadir in absolute neutrophil (ANC), white blood cell (WBC), and platelet measurements over all treatment cycles.

    2. Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts [Day 1 up to 125 weeks]

      Maximal degree of myelosuppression is represented by the nadir in hemoglobin (Hb) measurements over all treatment cycles.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    Patients had to meet the following criteria to be eligible for the study:

    1. Pathologically confirmed adenocarcinoma of the breast.

    2. No prior chemotherapy for metastatic breast cancer.

    3. Stage IV disease.

    4. Measurable disease (must have been ≥ 2.0 cm, except for pulmonary lesions that were well documented on CT scan that were ≥ 1.0 cm).

    5. At least 3 weeks since prior cytotoxic chemotherapy (patients should have recovered from all acute effects of such therapy.

    6. At least 4 weeks since radiotherapy, with full recovery. The measurable disease was completely outside the radiation portal or there was radiologic or clinical exam proof of progressive disease within the radiation portal.

    7. At least 4 weeks since major surgery, with full recovery.

    8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

    9. Age ≥18 years.

    10. Patient had the following blood counts at Baseline:

    • Absolute neutrophil count (ANC) ≥1.5*10^9 cells/L

    • Platelets ≥100*10^9 cells/L

    • Hemoglobin (Hgb) ≥9 g/dL.

    1. Patient had the following baseline blood chemistry levels:

    • Aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT])≥2.5x upper limit of normal (ULN) range

    • Total bilirubin normal

    • Alkaline phosphatase ≥2.5x ULN (unless bone metastasis is present in the absence of liver metastasis)

    • Creatinine ≥1.5 mg/dL.

    1. Peripheral neuropathy Grade 0 or 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

    2. If female of childbearing potential, pregnancy test was negative (within 72 hours of the first dose of study drug).

    3. If fertile, the patient agreed to use an effective method to avoid pregnancy for the duration of the study.

    4. Informed consent had been obtained.

    Exclusion Criteria:
    Patients who met any of the following criteria were excluded from the study:

    1. Prior neo-adjuvant or adjuvant chemotherapy was allowed. No prior chemotherapy for metastatic disease was allowed. If a taxane was part of the adjuvant regimen, at least one year should have transpired since completion of taxane regimen.

    2. Cumulative life-time dose of doxorubicin >360 mg/m^2. Doxorubicin was allowed as prior neo-adjuvant or adjuvant therapy but not for metastatic disease.

    3. Concurrent immunotherapy or hormonal therapy for breast cancer.

    4. Parenchymal brain metastases, unless documented to be clinically and radiographically stable for at least 6 months after treatment.

    5. Serious intercurrent medical or psychiatric illness, including serious active infection.

    6. History of class II-IV congestive heart failure.

    7. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.

    8. Patients who had received an investigational drug within the previous 3 weeks.

    9. Patient was enrolled in a different clinical study in which investigational procedures were performed or investigational therapies were administered. Also, a patient was not permitted enroll in such clinical trials while participating in this study.

    10. Pregnant or nursing women

    11. Patients with prior hypersensitivity to either Taxol or Taxotere.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Study Sites in Russia and the Ukraine Kiev Ukraine 01021

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Chair: Jose Iglesias, MD, Abraxis BioScience, LLC, a wholly owned subsidiary of Celgene Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00274456
    Other Study ID Numbers:
    • CA024
    First Posted:
    Jan 11, 2006
    Last Update Posted:
    Nov 21, 2019
    Last Verified:
    Nov 1, 2019
    Keywords provided by Celgene
    Metastatic breast cancer, nab paclitaxel, docetaxel,
    Additional relevant MeSH terms:
    Breast Neoplasms
    Paclitaxel
    Docetaxel
    Albumin-Bound Paclitaxel

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Three hundred and two patients were enrolled and randomized between November 2005 and June 2006, of which 300 received study drug and were evaluated for response and safety. Data below represents data cut-off 31 March 2008.
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Period Title: Overall Study
    STARTED 76 76 74 74
    At Least One Response Assessment 73 76 73 70
    COMPLETED 39 49 39 29
    NOT COMPLETED 37 27 35 45

    Baseline Characteristics

    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Docetaxel 100 mg/m^2 q3w Total
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest. Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w). Total of all reporting groups
    Overall Participants 76 76 74 74 300
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.7
    (9.47)
    55.4
    (9.59)
    53.3
    (9.14)
    55.4
    (11.57)
    53.9
    (10.05)
    Age, Customized (Number) [Number]
    >=65 years
    9
    11.8%
    14
    18.4%
    10
    13.5%
    19
    25.7%
    52
    17.3%
    <65 years
    67
    88.2%
    62
    81.6%
    64
    86.5%
    55
    74.3%
    248
    82.7%
    Sex: Female, Male (Count of Participants)
    Female
    76
    100%
    76
    100%
    74
    100%
    74
    100%
    300
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Number) [Number]
    White, Non-Hispanic, Non-Latino
    74
    97.4%
    75
    98.7%
    74
    100%
    74
    100%
    297
    99%
    White, Hispanic or Latino
    2
    2.6%
    1
    1.3%
    0
    0%
    0
    0%
    3
    1%
    Weight (Kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kg]
    72.56
    (12.668)
    73.64
    (14.670)
    76.24
    (13.437)
    75.99
    (14.034)
    74.59
    (13.742)
    Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
    0 (fully active)
    34
    44.7%
    33
    43.4%
    24
    32.4%
    28
    37.8%
    119
    39.7%
    1 (restrictive but ambulatory)
    35
    46.1%
    39
    51.3%
    45
    60.8%
    44
    59.5%
    163
    54.3%
    2 (ambulatory but unable to work)
    7
    9.2%
    4
    5.3%
    5
    6.8%
    2
    2.7%
    18
    6%
    3 (limited self-care) + 4 (completely disabled)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Menopausal Status (Number) [Number]
    Pre-menopausal
    26
    34.2%
    14
    18.4%
    21
    28.4%
    12
    16.2%
    73
    24.3%
    Post-menopausal
    49
    64.5%
    62
    81.6%
    53
    71.6%
    60
    81.1%
    224
    74.7%
    Unknown
    1
    1.3%
    0
    0%
    0
    0%
    2
    2.7%
    3
    1%
    Physician Assessment of Sensory Neuropathy (Number) [Number]
    Grade 0
    67
    88.2%
    70
    92.1%
    65
    87.8%
    67
    90.5%
    269
    89.7%
    Grade 1
    9
    11.8%
    6
    7.9%
    9
    12.2%
    7
    9.5%
    31
    10.3%
    Time from Primary Diagnosis and from First Metastasis/Relapse to Study Entry (Years) [Median (Full Range) ]
    Time from Primary Diagnosis to Study Entry
    1.24
    1.17
    0.97
    1.27
    1.23
    Time from First Metastasis/Relapse to Study Entry
    0.02
    0.04
    0.05
    0.04
    0.04
    Current Site of Metastasis/Relapse (Number) [Number]
    Breast
    10
    13.2%
    10
    13.2%
    11
    14.9%
    11
    14.9%
    42
    14%
    Skin/Soft Tissue
    16
    21.1%
    18
    23.7%
    15
    20.3%
    19
    25.7%
    68
    22.7%
    Supraclavicular
    23
    30.3%
    25
    32.9%
    20
    27%
    25
    33.8%
    93
    31%
    Axilla
    43
    56.6%
    48
    63.2%
    47
    63.5%
    44
    59.5%
    182
    60.7%
    Lung/Thoracic
    53
    69.7%
    49
    64.5%
    51
    68.9%
    58
    78.4%
    211
    70.3%
    Hepatic/Liver
    21
    27.6%
    28
    36.8%
    23
    31.1%
    25
    33.8%
    97
    32.3%
    Abdomen/Peritoneal
    12
    15.8%
    11
    14.5%
    4
    5.4%
    7
    9.5%
    34
    11.3%
    Pelvis
    0
    0%
    1
    1.3%
    2
    2.7%
    1
    1.4%
    4
    1.3%
    Bone
    22
    28.9%
    25
    32.9%
    33
    44.6%
    25
    33.8%
    105
    35%
    Other
    1
    1.3%
    4
    5.3%
    1
    1.4%
    1
    1.4%
    7
    2.3%
    Dominant Current Site of Metastasis/Relapse (Number) [Number]
    Visceral
    64
    84.2%
    61
    80.3%
    59
    79.7%
    67
    90.5%
    251
    83.7%
    Non-visceral
    12
    15.8%
    15
    19.7%
    15
    20.3%
    7
    9.5%
    49
    16.3%
    Stage at Primary Diagnosis (participants) [Number]
    Stage I
    2
    2.6%
    4
    5.3%
    3
    4.1%
    2
    2.7%
    11
    3.7%
    Stage IIa
    11
    14.5%
    13
    17.1%
    11
    14.9%
    13
    17.6%
    48
    16%
    Stage IIb
    12
    15.8%
    7
    9.2%
    13
    17.6%
    15
    20.3%
    47
    15.7%
    Stage IIIa
    11
    14.5%
    10
    13.2%
    7
    9.5%
    6
    8.1%
    34
    11.3%
    Stage IIIb
    14
    18.4%
    14
    18.4%
    9
    12.2%
    13
    17.6%
    50
    16.7%
    Stage IIIc
    0
    0%
    2
    2.6%
    0
    0%
    1
    1.4%
    3
    1%
    Stage IV
    23
    30.3%
    25
    32.9%
    28
    37.8%
    21
    28.4%
    97
    32.3%
    Unknown
    3
    3.9%
    1
    1.3%
    3
    4.1%
    3
    4.1%
    10
    3.3%
    Number of Lesions (Target + Non-Target) (Number) [Number]
    0 lesions
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1 lesion
    2
    2.6%
    1
    1.3%
    1
    1.4%
    4
    5.4%
    8
    2.7%
    2-3 lesions
    11
    14.5%
    13
    17.1%
    6
    8.1%
    10
    13.5%
    40
    13.3%
    >3 lesions
    63
    82.9%
    62
    81.6%
    67
    90.5%
    60
    81.1%
    252
    84%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator
    Description Percentage of participants who achieve an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms. A partial response (PR) is >= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR.
    Time Frame Day 1 up to 95 weeks

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all randomized participants who received at least one dose of study drug
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 76 76 74 74
    Independent reader assessed ORR
    37
    48.7%
    45
    59.2%
    49
    66.2%
    35
    47.3%
    Investigator assessed ORR
    46
    60.5%
    63
    82.9%
    74
    100%
    39
    52.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent reader assessed ORR. As per the protocol, if the conclusions from the investigator and independent assessments of response rate were the same, the investigator assessment was considered the primary analysis of response rate. If the conclusions were different, the independent radiology reader assessment was considered the primary analysis of response rate. The conclusions were different.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.224
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons were performed only if this test was significant.
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed ORR. As per the protocol, if the conclusions from the investigator and independent assessments of response rate were the same, the investigator assessment was considered the primary analysis of response rate. If the conclusions were different, the independent radiology reader assessment was considered the primary analysis of response rate. The conclusions were different.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons were performed only if this test was significant.
    Method Cochran-Mantel-Haenszel
    Comments CMH was stratified by study site
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessed ORR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed ORR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed ORR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly
    Comments Investigator assessed ORR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.024
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessed ORR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.099
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed ORR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    2. Secondary Outcome
    Title Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response
    Description Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately
    Time Frame Day 1 up to 95 weeks

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all randomized participants who received at least one dose of study drug
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 76 76 74 74
    Independent Assessed SD Disease Control
    68
    89.5%
    75
    98.7%
    80
    108.1%
    58
    78.4%
    Investigator Assessed Disease Control
    72
    94.7%
    83
    109.2%
    91
    123%
    69
    93.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly
    Comments Independent assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly
    Comments Independent assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 150 mg/m^2 Weekly
    Comments Independent assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.085
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed disease control rate (DCR), ie, SD >= 16 weeks, or CR or PR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparison was performed only if this test was significant.
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly
    Comments Investigator assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.098
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessed DCR
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test was stratified by study site.
    3. Secondary Outcome
    Title Kaplan-Meier Estimates for Progression-free Survival (PFS)
    Description PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
    Time Frame Day 1 up to 95 weeks

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all randomized participants who received at least one dose of study drug
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 76 76 74 74
    Independent Assessment for PFS
    11.0
    12.8
    12.9
    7.5
    Investigator Assessment for PFS
    10.9
    7.5
    14.6
    7.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0498
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons were performed only if this test was significant.
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0524
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.607
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0065
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.495
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 150 mg/m^2 Weekly
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons was performed only if this test was significant.
    Method Log Rank
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.568
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.972
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.076
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.702
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    4. Secondary Outcome
    Title Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression
    Description Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3.
    Time Frame Day 1 - 95 weeks

    Outcome Measure Data

    Analysis Population Description
    Patients with a confirmed CR or PR were included in this analysis. Patients who did not progress or die were censored at the last known time when patient was progression free. Patients who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 28 34 36 26
    Median (95% Confidence Interval) [months]
    13.0
    13.2
    15.1
    9.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Independent assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons was performed only if this test was significant.
    Method Log Rank
    Comments
    5. Secondary Outcome
    Title Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression
    Description Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3.
    Time Frame Day 1 - 95 weeks

    Outcome Measure Data

    Analysis Population Description
    Patients with a confirmed CR or PR were included in this analysis. Patients who did not progress or die were censored at the last known time when patient was progression free. Patients who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 35 48 55 29
    Median (95% Confidence Interval) [months]
    12.9
    9.2
    14.8
    15.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons was performed only if this test was significant.
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, Docetaxel 100 mg/m^2 q3w
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 150 mg/m^2 Weekly
    Comments Investigator assessment
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    6. Secondary Outcome
    Title Kaplan-Meier Estimate for Overall Survival (OS)
    Description Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010).
    Time Frame Day 1 to 221 weeks

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all randomized participants who received at least one dose of study drug
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 76 76 74 74
    Median (95% Confidence Interval) [months]
    27.7
    22.2
    33.8
    26.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons were performed only if this test was significant.
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, Docetaxel 100 mg/m^2 q3w
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection ABI-007 150 mg/m^2 Weekly, Docetaxel 100 mg/m^2 q3w
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 100 mg/m^2 Weekly
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.069
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.686
    Confidence Interval () 95%
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection ABI-007 300 mg/m^2 q3w, ABI-007 150 mg/m^2 Weekly
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection ABI-007 100 mg/m^2 Weekly, ABI-007 150 mg/m^2 Weekly
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.740
    Confidence Interval () 95%
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Other Pre-specified Outcome
    Title Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts
    Description Maximal degree of myelosuppression is represented by the nadir in absolute neutrophil (ANC), white blood cell (WBC), and platelet measurements over all treatment cycles.
    Time Frame Day 1 up to 125 weeks

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all randomized participants who received at least one dose of study drug, and had blood tests performed following treatment. Three participants dropped out after a single dose so have no post-treatment lab values.
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 75 76 74 72
    ANC
    1.21
    (1.004)
    1.51
    (0.960)
    1.11
    (0.628)
    0.38
    (0.339)
    WBC
    2.88
    (1.187)
    3.15
    (1.228)
    2.68
    (0.817)
    1.60
    (0.726)
    Platelet
    182.1
    (59.16)
    192.1
    (57.82)
    172.6
    (46.39)
    161.8
    (49.06)
    8. Secondary Outcome
    Title Participants With Treatment-Emergent, Treatment-Related Adverse Events
    Description Summary of participants who had treatment-emergent that were treatment-related in the opinion of the investigator, and summarized in a variety of categories. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death.
    Time Frame Day 1 up to 125 weeks

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all randomized participants who received at least one dose of study drug
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 76 76 74 74
    >= 1 adverse event (AE)
    75
    98.7%
    75
    98.7%
    73
    98.6%
    73
    98.6%
    >=1 treatment-related AE
    74
    97.4%
    72
    94.7%
    73
    98.6%
    72
    97.3%
    >=1 serious AE
    14
    18.4%
    12
    15.8%
    11
    14.9%
    56
    75.7%
    >=1 treatment-related serious AE
    13
    17.1%
    5
    6.6%
    8
    10.8%
    55
    74.3%
    >=1 severe (grade 3-5) treatment-related AE
    47
    61.8%
    30
    39.5%
    49
    66.2%
    71
    95.9%
    Grade 3-5 Neutropenia
    33
    43.4%
    19
    25%
    33
    44.6%
    68
    91.9%
    Grade 3-5 Febrile neutropenia
    1
    1.3%
    1
    1.3%
    1
    1.4%
    8
    10.8%
    Grade 3-5 Sensory neuropathy
    16
    21.1%
    7
    9.2%
    16
    21.6%
    9
    12.2%
    >=1 AE with outcome of death
    0
    0%
    1
    1.3%
    2
    2.7%
    2
    2.7%
    >=1 treatment-related AE with outcome of death
    0
    0%
    0
    0%
    0
    0%
    2
    2.7%
    >=1 treatment-related AE drug discontinued
    10
    13.2%
    5
    6.6%
    12
    16.2%
    16
    21.6%
    >=1 treatment-related AE drug dosage reduced
    14
    18.4%
    13
    17.1%
    35
    47.3%
    21
    28.4%
    >=1 treatment-related AE drug interrupted
    1
    1.3%
    1
    1.3%
    0
    0%
    1
    1.4%
    9. Other Pre-specified Outcome
    Title Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts
    Description Maximal degree of myelosuppression is represented by the nadir in hemoglobin (Hb) measurements over all treatment cycles.
    Time Frame Day 1 up to 125 weeks

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all randomized participants who received at least one dose of study drug, and had blood tests performed following treatment. Three participants dropped out after a single dose so have no post-treatment lab values.
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    Measure Participants 75 76 74 72
    Mean (Standard Deviation) [g/L]
    112.1
    (10.58)
    106.7
    (10.72)
    105.6
    (11.31)
    107.1
    (13.39)

    Adverse Events

    Time Frame Day 1 up to 125 weeks
    Adverse Event Reporting Description Treatment-emergent AEs defined as AEs that begin or worsen in grade after the first dose of study drug through 30 days after the last dose of study drug.
    Arm/Group Title ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Arm/Group Description ABI-007 300 mg/m^2 administered once every third week (q3w). ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w).
    All Cause Mortality
    ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/76 (18.4%) 12/76 (15.8%) 11/74 (14.9%) 56/74 (75.7%)
    Blood and lymphatic system disorders
    Neutropenia 10/76 (13.2%) 2/76 (2.6%) 4/74 (5.4%) 52/74 (70.3%)
    Febrile neutropenia 1/76 (1.3%) 1/76 (1.3%) 1/74 (1.4%) 8/74 (10.8%)
    Anaemia 0/76 (0%) 0/76 (0%) 1/74 (1.4%) 0/74 (0%)
    Thrombocytopenia 0/76 (0%) 0/76 (0%) 0/74 (0%) 1/74 (1.4%)
    Cardiac disorders
    Cardiopulmonary failure 0/76 (0%) 1/76 (1.3%) 1/74 (1.4%) 0/74 (0%)
    Eye disorders
    Optic ischaemic neuropathy 0/76 (0%) 1/76 (1.3%) 0/74 (0%) 0/74 (0%)
    Gastrointestinal disorders
    Bowel peristalsis increased 1/76 (1.3%) 0/76 (0%) 0/74 (0%) 0/74 (0%)
    Colitis 0/76 (0%) 1/76 (1.3%) 0/74 (0%) 0/74 (0%)
    Diarrhoea 0/76 (0%) 0/76 (0%) 0/74 (0%) 1/74 (1.4%)
    Gastritis 0/76 (0%) 0/76 (0%) 0/74 (0%) 1/74 (1.4%)
    Nausea 0/76 (0%) 1/76 (1.3%) 0/74 (0%) 0/74 (0%)
    General disorders
    Inflammation localised 0/76 (0%) 0/76 (0%) 1/74 (1.4%) 0/74 (0%)
    Hepatobiliary disorders
    Jaundice 0/76 (0%) 0/76 (0%) 0/74 (0%) 1/74 (1.4%)
    Immune system disorders
    Hypersensitivity 0/76 (0%) 1/76 (1.3%) 0/74 (0%) 0/74 (0%)
    Infections and infestations
    Erysipelas 0/76 (0%) 2/76 (2.6%) 0/74 (0%) 1/74 (1.4%)
    Chronic sinusitis 0/76 (0%) 0/76 (0%) 1/74 (1.4%) 0/74 (0%)
    Investigations
    Body temperature increased 0/76 (0%) 0/76 (0%) 0/74 (0%) 1/74 (1.4%)
    Liver function test abnormal 1/76 (1.3%) 0/76 (0%) 0/74 (0%) 0/74 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/76 (0%) 0/76 (0%) 0/74 (0%) 1/74 (1.4%)
    Hypercalcaemia 1/76 (1.3%) 0/76 (0%) 0/74 (0%) 0/74 (0%)
    Nervous system disorders
    Convulsion 0/76 (0%) 1/76 (1.3%) 0/74 (0%) 0/74 (0%)
    Renal and urinary disorders
    Urinary retention 0/76 (0%) 1/76 (1.3%) 0/74 (0%) 0/74 (0%)
    Skin and subcutaneous tissue disorders
    Rash 0/76 (0%) 0/76 (0%) 1/74 (1.4%) 0/74 (0%)
    Vascular disorders
    Lymphocele 0/76 (0%) 1/76 (1.3%) 0/74 (0%) 0/74 (0%)
    Thrombophlebitis 0/76 (0%) 0/76 (0%) 1/74 (1.4%) 0/74 (0%)
    Other (Not Including Serious) Adverse Events
    ABI-007 300 mg/m^2 q3w ABI-007 100 mg/m^2 Weekly ABI-007 150 mg/m^2 Weekly Docetaxel 100 mg/m^2 q3w
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 75/76 (98.7%) 75/76 (98.7%) 73/74 (98.6%) 73/74 (98.6%)
    Blood and lymphatic system disorders
    Neutropenia 31/76 (40.8%) 22/76 (28.9%) 38/74 (51.4%) 55/74 (74.3%)
    Leukopenia 9/76 (11.8%) 3/76 (3.9%) 4/74 (5.4%) 17/74 (23%)
    Anaemia 2/76 (2.6%) 3/76 (3.9%) 6/74 (8.1%) 5/74 (6.8%)
    Gastrointestinal disorders
    Nausea 13/76 (17.1%) 8/76 (10.5%) 16/74 (21.6%) 15/74 (20.3%)
    Diarrhoea 6/76 (7.9%) 7/76 (9.2%) 10/74 (13.5%) 15/74 (20.3%)
    Stomatitis 3/76 (3.9%) 1/76 (1.3%) 0/74 (0%) 16/74 (21.6%)
    Vomiting 6/76 (7.9%) 3/76 (3.9%) 3/74 (4.1%) 4/74 (5.4%)
    Abdominal pain 6/76 (7.9%) 3/76 (3.9%) 4/74 (5.4%) 1/74 (1.4%)
    Abdominal pain upper 1/76 (1.3%) 1/76 (1.3%) 3/74 (4.1%) 4/74 (5.4%)
    General disorders
    Asthenia 22/76 (28.9%) 18/76 (23.7%) 22/74 (29.7%) 30/74 (40.5%)
    Oedema peripheral 7/76 (9.2%) 13/76 (17.1%) 16/74 (21.6%) 18/74 (24.3%)
    Performance status decreased 10/76 (13.2%) 18/76 (23.7%) 10/74 (13.5%) 14/74 (18.9%)
    Fatigue 11/76 (14.5%) 11/76 (14.5%) 14/74 (18.9%) 14/74 (18.9%)
    Pyrexia 4/76 (5.3%) 5/76 (6.6%) 3/74 (4.1%) 5/74 (6.8%)
    Infections and infestations
    Respiratory tract infection viral 4/76 (5.3%) 3/76 (3.9%) 3/74 (4.1%) 6/74 (8.1%)
    Respiratory tract infection 2/76 (2.6%) 1/76 (1.3%) 6/74 (8.1%) 1/74 (1.4%)
    Investigations
    Gamma glutamyl transferase increased 5/76 (6.6%) 3/76 (3.9%) 3/74 (4.1%) 5/74 (6.8%)
    Alanine aminotransferase increased 8/76 (10.5%) 2/76 (2.6%) 2/74 (2.7%) 1/74 (1.4%)
    Aspartate aminotransferase increased 7/76 (9.2%) 1/76 (1.3%) 3/74 (4.1%) 1/74 (1.4%)
    Body temperature increased 4/76 (5.3%) 1/76 (1.3%) 3/74 (4.1%) 4/74 (5.4%)
    Metabolism and nutrition disorders
    Anorexia 3/76 (3.9%) 2/76 (2.6%) 4/74 (5.4%) 7/74 (9.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 26/76 (34.2%) 16/76 (21.1%) 26/74 (35.1%) 17/74 (23%)
    Myalgia 13/76 (17.1%) 6/76 (7.9%) 13/74 (17.6%) 10/74 (13.5%)
    Pain in extremity 5/76 (6.6%) 6/76 (7.9%) 7/74 (9.5%) 7/74 (9.5%)
    Bone pain 5/76 (6.6%) 3/76 (3.9%) 1/74 (1.4%) 3/74 (4.1%)
    Nervous system disorders
    Peripheral sensory neuropathy 33/76 (43.4%) 30/76 (39.5%) 45/74 (60.8%) 29/74 (39.2%)
    Neuropathy 19/76 (25%) 10/76 (13.2%) 9/74 (12.2%) 15/74 (20.3%)
    Neuropathy peripheral 5/76 (6.6%) 6/76 (7.9%) 13/74 (17.6%) 7/74 (9.5%)
    Headache 3/76 (3.9%) 11/76 (14.5%) 7/74 (9.5%) 6/74 (8.1%)
    Hypoaesthesia 7/76 (9.2%) 4/76 (5.3%) 3/74 (4.1%) 3/74 (4.1%)
    Peripheral motor neuropathy 5/76 (6.6%) 0/76 (0%) 5/74 (6.8%) 6/74 (8.1%)
    Paraesthesia 3/76 (3.9%) 5/76 (6.6%) 3/74 (4.1%) 3/74 (4.1%)
    Dizziness 1/76 (1.3%) 3/76 (3.9%) 4/74 (5.4%) 0/74 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/76 (1.3%) 5/76 (6.6%) 5/74 (6.8%) 3/74 (4.1%)
    Cough 2/76 (2.6%) 3/76 (3.9%) 4/74 (5.4%) 0/74 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 51/76 (67.1%) 59/76 (77.6%) 59/74 (79.7%) 52/74 (70.3%)
    Nail disorder 3/76 (3.9%) 8/76 (10.5%) 20/74 (27%) 10/74 (13.5%)
    Rash 5/76 (6.6%) 3/76 (3.9%) 3/74 (4.1%) 4/74 (5.4%)
    Pruritus 3/76 (3.9%) 0/76 (0%) 5/74 (6.8%) 2/74 (2.7%)
    Skin hyperpigmentation 0/76 (0%) 1/76 (1.3%) 5/74 (6.8%) 2/74 (2.7%)
    Skin toxicity 0/76 (0%) 0/76 (0%) 2/74 (2.7%) 4/74 (5.4%)
    Vascular disorders
    Hyperaemia 2/76 (2.6%) 2/76 (2.6%) 1/74 (1.4%) 8/74 (10.8%)
    Hypertension 1/76 (1.3%) 5/76 (6.6%) 4/74 (5.4%) 2/74 (2.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Publications of this multicenter trial should include input from INVESTIGATORS, his/her colleagues, and SPONSOR personnel. Such input should be reflected in publication authorship, and agreement regarding order of authors should be established before writing a manuscript. Subsequent to the multicenter publication or one year after completion of the study, whichever occurs first, an investigator and/or his/her colleagues may publish the results of INVESTIGATOR's part of the study independently.

    Results Point of Contact

    Name/Title Associate Director, Clinical Trials Disclosure
    Organization Celgene Corporation
    Phone 1-888-260-1599
    Email clinicaltrialdisclosure@celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00274456
    Other Study ID Numbers:
    • CA024
    First Posted:
    Jan 11, 2006
    Last Update Posted:
    Nov 21, 2019
    Last Verified:
    Nov 1, 2019