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Docetaxel and Prednisone With or Without Bevacizumab in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00110214
Collaborator
(none)
1,050
Enrollment
2
Locations
2
Arms
76
Duration (Months)
525
Patients Per Site
6.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase III trial is studying docetaxel, prednisone, and bevacizumab to see how well they work compared to docetaxel and prednisone in treating patients with prostate cancer that did not respond to hormone therapy. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether docetaxel, prednisone, and bevacizumab are more effective than docetaxel and prednisone in treating prostate cancer.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine if the addition of bevacizumab to docetaxel and prednisone increases overall survival compared to docetaxel and prednisone alone in patients with HRPC.
SECONDARY OBJECTIVES:

  1. To compare the progression-free survival of these two regimens in patients with HRPC.

  2. To compare the two regimens on the proportion of patients who experience a 50% post-therapy PSA decline from baseline.

  3. To compare the two regimens with respect to the proportion of patients who experience grade 3 or higher toxicities.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to predicted 24-month survival probability (< 10% vs 10-29.9% vs ≥ 30%), age (< 65 years vs ≥ 65 years), and prior history of arterial events (i.e., cardiac ischemia/infarction, CNS cerebrovascular ischemia, peripheral arterial ischemia, or CNS hemorrhage) (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel IV over 1 hour and placebo IV over 30-90 minutes on day 1. Patients also receive oral prednisone once daily on days 1-21.

ARM II: Patients receive docetaxel and prednisone as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1.

In both arms, courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
1050 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized Double-Blinded Placebo Controlled Phase III Trial Comparing Doctaxel and Prednisone With and Without Bevacizumab (IND #7921, NSC #704865) in Men With Hormone Refractory Prostate Cancer
Study Start Date :
Apr 1, 2005
Actual Primary Completion Date :
Mar 1, 2010
Actual Study Completion Date :
Aug 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I

Patients receive docetaxel IV over 1 hour and placebo IV over 30-90 minutes on day 1. Patients also receive oral prednisone once daily on days 1-21.

Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT

    • Other: placebo
    Given IV
    Other Names:
  • PLCB

    • Drug: prednisone
    Given orally
    Other Names:
  • DeCortin
  • Deltra

    • Other: laboratory biomarker analysis
    Correlative studies
    Experimental: Arm II

    Patients receive docetaxel and prednisone as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1.

    Drug: docetaxel
    Given IV
    Other Names:
  • RP 56976
  • Taxotere
  • TXT

    • Drug: prednisone
    Given orally
    Other Names:
  • DeCortin
  • Deltra

    • Biological: bevacizumab
    Given IV
    Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

    • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [Duration of study (up to 5 years)]

      Overall Survival (OS) was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method.

    Secondary Outcome Measures

    1. Proportion of Participants Who Experienced at Least a 50% Post-therapy PSA (Prostate-Specific Antigen) Decline [Duration of study (up to 5 years)]

      PSA decline will be reported on all patients and will be defined as a decrease in PSA value by >= 50% for two successive evaluations at least 4 weeks apart. The reference PSA value for these declines should be measured within 2 weeks before starting therapy.

    2. Progression-free Survival (PFS) [Duration of study (up to 5 years)]

      PFS was defined as the data of randomization to date of progression or death due to any cause, whichever occurs first. PFS was estimated using the Kaplan Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    3. Proportion of Participants Who Experience (Maximum) Grade 3 or Higher Toxicities [During treatment (up to 2 years)]

      The National Cancer Institute (NCI) Criteria for Adverse Events(CTCAE) Version 3.0 was used to evaluate toxicity. These events were considered at least possibly related to treatment. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic (clinically metastatic disease documented on bone, CT or MRI scan) disease despite castrate levels of testosterone due to orchiectomy or LHRH agonist; castrate levels of testosterone must be maintained

    • All eligible patients must have a Gleason sum based on biopsy or TURP at the time of registration

    • At the time of enrollment, patients must have evidence of progressive metastatic disease, either:

    • Measurable disease with any level of serum PSA OR

    • Non-measurable disease with PSA ≥ 5 ng/ml; patients with PSA ≥ 5 ng/ml only and no other radiographic evidence of metastatic prostate cancer are not eligible

    • Definition of Measurable Disease/Target Lesions:

    • Any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques: 1) physical exam for clinically palpable lymph nodes and superficial skin lesions, 2) chest X-ray for clearly defined lung lesions surrounded by aerated lung OR those lesions measured as ≥ 10 mm with a spiral CT or MRI scan

    • Measurable lesions (up to a maximum of 10 in number) representative of all organs involved to be identified as target lesions; the sum of the longest diameters (LD) for all target lesions will be calculated and reported as baseline sum LD

    • If measurable disease is confined to a solitary lesion and is not consistent with prostate cancer, then its neoplastic nature must be confirmed by histology

    • Ultrasound may not be used to measure tumor lesions that are not easily accessible clinically

    • Definition of Non-measurable Disease/Non-target Lesions:

    • Non-target lesions include all other lesions not included in above, including small lesions with longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan and truly non-measurable lesions, which include:

    • Bone lesions

    • Pleural or pericardial effusions, ascites

    • CNS lesions, leptomeningeal disease

    • Irradiated lesions, unless progression documented after RT

    • Patients must have demonstrated evidence of progressive disease since the most recent change in therapy; progressive disease is defined as any one of the following (measurable disease, bone scan, or PSA progression):

    • Measurable Disease Progression: Objective evidence of increase > 20% in the sum of the longest diameters (LD) of target lesions from the time of maximal regression or the appearance of one or more new lesions

    • Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer along with a PSA ≥ 5 ng/ml will constitute progression

    • PSA Progression: An elevated PSA (≥ 5 ng/mL) which has risen serially on at least two occasions after the discontinuation of antiandrogen therapy, each at least one week apart; if the confirmatory PSA (#3) value is less than screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression

    • The reference PSA value (#1) must be measured at the time of the discontinuation of antiandrogen therapy; and at least 2 PSA measurements must be made following the end of antiandrogen therapy and prior to registration

    • (For the purposes of the nomogram calculator, the last PSA value recorded prior to the initiation of treatment will be considered the baseline PSA)

    • Progression despite standard androgen deprivation therapy (i.e., LHRH agonist and/or orchiectomy)

    • All antiandrogens (e.g., flutamide, megestrol acetate [even if taken for hot flashes], bicalutamide and nilutamide) of any dose must be discontinued at least 4 weeks prior to registration; if improvement following antiandrogen withdrawal is noted, progression must be established using the criteria above

    • Primary testicular androgen suppression (e.g., with an LHRH agonist) should not be discontinued

    • At least 4 weeks since any other hormonal therapy, including ketoconazole and aminoglutethimide; the only exception to this time frame is that 5α-reductase inhibitors (e.g., finasteride, dutasteride) may be discontinued any time prior to registration

    • No prior cytotoxic chemotherapy, including estramustine or suramin

    • No prior anti-angiogenesis agents, including thalidomide and bevacizumab

    • ≥ 4 weeks since major surgery and fully recovered

    • ≥ 4 weeks since any prior radiation (including palliative) and fully recovered

    • ≥ 8 weeks since the last dose of Strontium-89 or Samarium

    • Patients receiving a bisphosphonate must be on a stable dose and must have started the bisphosphonate ≥ 4 weeks prior to initiating protocol treatment. Patients do not have to be on a bisphosphonate to qualify for the study; patients may initiate bisphosphonate therapy after completion of Cycle 1, if clinically indicated

    • Patients enrolled on CALGB 90202 who have documented disease progression and have received at least 4 weeks of open label zoledronic acid treatment, are eligible for this study.

    • No known brain metastases (brain imaging (MRI/CT) is not required)

    • No current congestive heart failure (New York Heart Association Class II, III or IV)

    • Patients with history of hypertension must be well controlled (< 160/90) on a regimen of anti-hypertensive therapy

    • Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range INR (usually between 2 and 3) or be on a stable dose of LMW heparin; patients receiving anti-platelet agents are also eligible; in addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible

    • No significant history of bleeding events or GI perforation

    • Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6 months of registration are not eligible

    • Patients with a history of GI perforation within 12 months of registration are not eligible.

    • No recent (within 12 months) arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina or angina requiring surgical or medical intervention in the past 12 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) or any other arterial thrombotic event are also ineligible

    • No serious or non-healing wound, ulcer or bone fracture

    • No peripheral neuropathy ≥ grade 2

    • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible

    • PC-Spes, Saw Palmetto, and St. John's Wort must be discontinued before registration; the discontinuation of other herbal medications and food supplements is strongly encouraged; patients may continue on daily vitamins and calcium supplements

    • ECOG performance status: 0-2

    • ANC ≥ 1500/μL

    • Platelet count ≥ 100,000/μL

    • Creatinine ≤ 1.5 x upper limits of normal

    • Bilirubin ≤ 1.5 x upper limits of normal

    • For patients with Gilbert's Disease, ≤ 2.5 X ULN is allowed

    • AST ≤ 1.5 x upper limits of normal

    • PSA ≥ 5 ng/mL (if non-measurable disease)

    • Urine protein to creatinine ratio < 1.0

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Yale University New Haven Connecticut United States 06520
    2 Cancer and Leukemia Group B Chicago Illinois United States 60606

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: William Kelly, Cancer and Leukemia Group B

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00110214
    Other Study ID Numbers:
    • NCI-2012-02814
    • NCI-2012-02814
    • CDR0000427290
    • CALGB-90401
    • CALGB-90401
    • P30CA014236
    • U10CA031946
    First Posted:
    May 5, 2005
    Last Update Posted:
    May 9, 2014
    Last Verified:
    Dec 1, 2012
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Prednisone
    Bevacizumab
    Antineoplastic Agents, Immunological
    Docetaxel
    Antibodies
    Immunoglobulins
    Antibodies, Monoclonal

    Study Results

    Participant Flow

    Recruitment Details Between May 2005 and December 2007, 1,050 participants were recruited and randomized
    Pre-assignment Detail
    Arm/Group Title Docetaxel + Placebo Docetaxel + Bevacizumab
    Arm/Group Description Standard treatment Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Placebo Std Tx + monoclonal antibody therapy Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Bevacizumab: 15 mg/kg IV every 3 weeks
    Period Title: Overall Study
    STARTED 526 524
    COMPLETED 17 21
    NOT COMPLETED 509 503

    Baseline Characteristics

    Arm/Group Title Docetaxel + Placebo Docetaxel + Bevacizumab Total
    Arm/Group Description Standard treatment Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Placebo Std Tx + monoclonal antibody therapy Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Bevacizumab: 15 mg/kg IV every 3 weeks Total of all reporting groups
    Overall Participants 526 524 1050
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    69.3
    68.8
    69.0
    Age, Customized (participants) [Number]
    < 65 years
    174
    33.1%
    179
    34.2%
    353
    33.6%
    >=65 years
    352
    66.9%
    345
    65.8%
    697
    66.4%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    526
    100%
    524
    100%
    1050
    100%
    Region of Enrollment (participants) [Number]
    United States
    526
    100%
    524
    100%
    1050
    100%
    24-month predicted survival probability (participants) [Number]
    <10%
    95
    18.1%
    94
    17.9%
    189
    18%
    10-29.9%
    184
    35%
    183
    34.9%
    367
    35%
    >=30%
    247
    47%
    247
    47.1%
    494
    47%
    Prior history of arterial events (participants) [Number]
    Yes
    42
    8%
    37
    7.1%
    79
    7.5%
    No
    484
    92%
    487
    92.9%
    971
    92.5%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival
    Description Overall Survival (OS) was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method.
    Time Frame Duration of study (up to 5 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Docetaxel + Placebo Docetaxel + Bevacizumab
    Arm/Group Description Standard treatment Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Placebo Std Tx + monoclonal antibody therapy Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Bevacizumab: 15 mg/kg IV every 3 weeks
    Measure Participants 526 524
    Median (95% Confidence Interval) [months]
    21.5
    22.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Docetaxel + Placebo, Docetaxel + Bevacizumab
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Superiority and futility analyses were conducted for the OS end point. The Lan-Demets analog of the Emerson-Fleming sequential boundary was used to maintain the overall significance level of alpha=0.05 while conducting interim analyses on OS. The final analysis was performed when 748 deaths had been observed. An intention-to-treat approach was used in the analysis for all the clinical end points with the exception of toxicity.
    Statistical Test of Hypothesis p-Value 0.181
    Comments The primary analysis was adjusted for the stratification factors (24-mo survival probability as predicted by a validated nomogram (<10%,10%-29.9%,>=30%), age (<65, >=65 years) and prior history of arterial events (yes, no)).
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.91
    Confidence Interval (2-Sided) 95%
    0.7 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Proportion of Participants Who Experienced at Least a 50% Post-therapy PSA (Prostate-Specific Antigen) Decline
    Description PSA decline will be reported on all patients and will be defined as a decrease in PSA value by >= 50% for two successive evaluations at least 4 weeks apart. The reference PSA value for these declines should be measured within 2 weeks before starting therapy.
    Time Frame Duration of study (up to 5 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Docetaxel + Placebo Docetaxel + Bevacizumab
    Arm/Group Description Standard treatment Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Placebo Std Tx + monoclonal antibody therapy Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Bevacizumab: 15 mg/kg IV every 3 weeks
    Measure Participants 526 524
    Number [percentage of participants]
    57.9
    11%
    69.5
    13.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Docetaxel + Placebo, Docetaxel + Bevacizumab
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Chi-squared
    Comments
    3. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description PFS was defined as the data of randomization to date of progression or death due to any cause, whichever occurs first. PFS was estimated using the Kaplan Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
    Time Frame Duration of study (up to 5 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Docetaxel + Placebo Docetaxel + Bevacizumab
    Arm/Group Description Standard treatment Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Placebo Std Tx + monoclonal antibody therapy Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Bevacizumab: 15 mg/kg IV every 3 weeks
    Measure Participants 526 524
    Median (95% Confidence Interval) [months]
    7.5
    9.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Docetaxel + Placebo, Docetaxel + Bevacizumab
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The primary analysis was adjusted for the stratification factors (24-mo survival probability as predicted by a validated nomogram (<10%,10%-29.9%,>=30%), age (<65, >=65 years) and prior history of arterial events (yes, no)).
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.80
    Confidence Interval (2-Sided) 95%
    0.71 to 0.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Proportion of Participants Who Experience (Maximum) Grade 3 or Higher Toxicities
    Description The National Cancer Institute (NCI) Criteria for Adverse Events(CTCAE) Version 3.0 was used to evaluate toxicity. These events were considered at least possibly related to treatment. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death
    Time Frame During treatment (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    Participants who did not received allocated intervention were excluded from toxicity analysis.
    Arm/Group Title Docetaxel + Placebo Docetaxel + Bevacizumab
    Arm/Group Description Standard treatment Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Placebo Std Tx + monoclonal antibody therapy Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Bevacizumab: 15 mg/kg IV every 3 weeks
    Measure Participants 505 504
    Number [percentage of participants]
    56.2
    10.7%
    75.4
    14.4%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Participants who did not received allocated intervention were excluded from toxicity analysis
    Arm/Group Title Docetaxel + Placebo Docetaxel + Bevacizumab
    Arm/Group Description Standard treatment Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Placebo Std Tx + monoclonal antibody therapy Docetaxel: 75 mg/m2 by IV over 1 hour for 21 days, Prednisone: 5mg orally twice per day Bevacizumab: 15 mg/kg IV every 3 weeks
    All Cause Mortality
    Docetaxel + Placebo Docetaxel + Bevacizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Docetaxel + Placebo Docetaxel + Bevacizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 237/505 (46.9%) 178/504 (35.3%)
    Blood and lymphatic system disorders
    DIC (disseminated intravascular coagulation) 0/505 (0%) 0 1/504 (0.2%) 1
    Febrile neutropenia 25/505 (5%) 26 19/504 (3.8%) 21
    Hemoglobin 17/505 (3.4%) 19 14/504 (2.8%) 15
    Lymphatics - Other 0/505 (0%) 0 1/504 (0.2%) 1
    Cardiac disorders
    Cardiac Arrhythmia - Other 1/505 (0.2%) 1 1/504 (0.2%) 1
    Cardiac General - Other 1/505 (0.2%) 1 1/504 (0.2%) 1
    Cardiac ischemia/infarction 12/505 (2.4%) 12 4/504 (0.8%) 4
    Cardiopulmonary arrest cause unknown (non-fatal) 1/505 (0.2%) 1 0/504 (0%) 0
    Conduction abnormality/atrioventricular heart block 0/505 (0%) 0 2/504 (0.4%) 3
    Left ventricular diastolic dysfunction 0/505 (0%) 0 2/504 (0.4%) 3
    Left ventricular systolic dysfunction 2/505 (0.4%) 2 1/504 (0.2%) 1
    Supraventricular and nodal arrhythmia 8/505 (1.6%) 8 10/504 (2%) 11
    Ventricular arrhythmia 1/505 (0.2%) 1 1/504 (0.2%) 1
    Endocrine disorders
    Thyroid function high (hyperthyroidism thyrotoxicosis) 0/505 (0%) 0 1/504 (0.2%) 1
    Eye disorders
    Ocular/Visual - Other 0/505 (0%) 0 1/504 (0.2%) 1
    Vision-blurred vision 0/505 (0%) 0 1/504 (0.2%) 1
    Watery eye (epiphora tearing) 2/505 (0.4%) 2 0/504 (0%) 0
    Gastrointestinal disorders
    Colitis 2/505 (0.4%) 2 1/504 (0.2%) 1
    Constipation 2/505 (0.4%) 2 3/504 (0.6%) 3
    Diarrhea 13/505 (2.6%) 13 9/504 (1.8%) 10
    Enteritis (inflammation of the small bowel) 2/505 (0.4%) 2 0/504 (0%) 0
    Esophagitis 2/505 (0.4%) 2 0/504 (0%) 0
    Fistula, GI 6/505 (1.2%) 6 2/504 (0.4%) 3
    Gastritis (including bile reflux gastritis) 1/505 (0.2%) 1 0/504 (0%) 0
    Gastrointestinal - Other 4/505 (0.8%) 4 1/504 (0.2%) 1
    Heartburn/dyspepsia 1/505 (0.2%) 1 0/504 (0%) 0
    Hemorrhage, GI 38/505 (7.5%) 42 18/504 (3.6%) 19
    Mucositis/stomatitis (clinical exam) 1/505 (0.2%) 1 1/504 (0.2%) 1
    Mucositis/stomatitis (functional/symptomatic) 8/505 (1.6%) 9 0/504 (0%) 0
    Nausea 16/505 (3.2%) 18 5/504 (1%) 5
    Obstruction GI 2/505 (0.4%) 2 1/504 (0.2%) 1
    Perforation, GI 19/505 (3.8%) 20 3/504 (0.6%) 3
    Proctitis 0/505 (0%) 0 1/504 (0.2%) 1
    Ulcer GI 1/505 (0.2%) 1 1/504 (0.2%) 1
    Ulcer, GI 4/505 (0.8%) 5 1/504 (0.2%) 2
    Vomiting 10/505 (2%) 10 4/504 (0.8%) 4
    General disorders
    Death not associated with CTCAE term 10/505 (2%) 10 10/504 (2%) 10
    Edema: limb 1/505 (0.2%) 1 2/504 (0.4%) 2
    Fatigue (asthenia, lethargy, malaise) 39/505 (7.7%) 46 22/504 (4.4%) 27
    Fever 43/505 (8.5%) 47 32/504 (6.3%) 35
    Injection site reaction/extravasation changes 1/505 (0.2%) 1 0/504 (0%) 0
    Pain - Other 5/505 (1%) 6 3/504 (0.6%) 3
    Rigors/chills 13/505 (2.6%) 15 17/504 (3.4%) 20
    Hepatobiliary disorders
    Cholecystitis 3/505 (0.6%) 3 0/504 (0%) 0
    Necrosis GI 1/505 (0.2%) 1 0/504 (0%) 0
    Necrosis, GI 1/505 (0.2%) 1 0/504 (0%) 0
    Obstruction, GI 1/505 (0.2%) 1 0/504 (0%) 0
    Immune system disorders
    Allergic reaction/hypersensitivity (including drug fever) 3/505 (0.6%) 3 3/504 (0.6%) 3
    Infections and infestations
    Colitis, infectious (e.g., Clostridium difficile) 3/505 (0.6%) 3 2/504 (0.4%) 3
    Infection 35/505 (6.9%) 41 27/504 (5.4%) 30
    Infection - Other 14/505 (2.8%) 14 4/504 (0.8%) 4
    Infection with normal ANC or Grade 1 or 2 neutrophils 18/505 (3.6%) 19 11/504 (2.2%) 15
    Infection with unknown ANC 13/505 (2.6%) 13 3/504 (0.6%) 3
    Infection without neutropenia 2/505 (0.4%) 2 0/504 (0%) 0
    Opportunistic infection associated with >=Grade 2 Lymphopenia 2/505 (0.4%) 2 1/504 (0.2%) 1
    Injury, poisoning and procedural complications
    Fracture 4/505 (0.8%) 4 1/504 (0.2%) 2
    Thrombosis/embolism (vascular access-related) 1/505 (0.2%) 1 0/504 (0%) 0
    Wound complication non-infectious 1/505 (0.2%) 1 0/504 (0%) 0
    Investigations
    ALT, SGPT (serum glutamic pyruvic transaminase) 1/505 (0.2%) 1 0/504 (0%) 0
    AST, SGOT(serum glutamic oxaloacetic transaminase) 2/505 (0.4%) 2 1/504 (0.2%) 1
    Alkaline phosphatase 1/505 (0.2%) 1 1/504 (0.2%) 1
    Bilirubin (hyperbilirubinemia) 1/505 (0.2%) 1 0/504 (0%) 0
    Cardiac troponin I (cTnI) 4/505 (0.8%) 4 1/504 (0.2%) 1
    Cardiac troponin T (cTnT) 1/505 (0.2%) 1 0/504 (0%) 0
    Coagulation - Other 1/505 (0.2%) 1 0/504 (0%) 0
    Creatinine 2/505 (0.4%) 3 2/504 (0.4%) 2
    Fibrinogen 1/505 (0.2%) 1 0/504 (0%) 0
    INR (International Normalized Ratio of prothrombin time) 0/505 (0%) 0 1/504 (0.2%) 1
    Leukocytes (total WBC) 39/505 (7.7%) 48 25/504 (5%) 28
    Lymphopenia 11/505 (2.2%) 14 11/504 (2.2%) 14
    Metabolic/Laboratory - Other 0/505 (0%) 0 2/504 (0.4%) 2
    Neutrophils/granulocytes (ANC/AGC) 67/505 (13.3%) 79 46/504 (9.1%) 58
    Neutrophils/granulocytes (ANC/AGC) for BMT studies if specified in the protocol. 0/505 (0%) 0 1/504 (0.2%) 1
    PTT (Partial Thromboplastin Time) 1/505 (0.2%) 1 2/504 (0.4%) 2
    Platelets 2/505 (0.4%) 3 0/504 (0%) 0
    Weight gain 1/505 (0.2%) 3 0/504 (0%) 0
    Weight loss 2/505 (0.4%) 2 0/504 (0%) 0
    Metabolism and nutrition disorders
    Acidosis (metabolic or respiratory) 1/505 (0.2%) 1 0/504 (0%) 0
    Albumin, serum-low (hypoalbuminemia) 4/505 (0.8%) 4 2/504 (0.4%) 2
    Anorexia 14/505 (2.8%) 15 5/504 (1%) 5
    Calcium serum-high (hypercalcemia) 1/505 (0.2%) 1 0/504 (0%) 0
    Calcium serum-low (hypocalcemia) 5/505 (1%) 7 5/504 (1%) 5
    Dehydration 27/505 (5.3%) 32 14/504 (2.8%) 17
    Glucose serum-high (hyperglycemia) 11/505 (2.2%) 12 6/504 (1.2%) 8
    Glucose serum-low (hypoglycemia) 1/505 (0.2%) 1 3/504 (0.6%) 3
    Phosphate serum-low (hypophosphatemia) 4/505 (0.8%) 5 4/504 (0.8%) 4
    Potassium serum-high (hyperkalemia) 2/505 (0.4%) 2 1/504 (0.2%) 1
    Potassium serum-low (hypokalemia) 4/505 (0.8%) 4 5/504 (1%) 6
    Sodium serum-low (hyponatremia) 10/505 (2%) 10 6/504 (1.2%) 6
    Musculoskeletal and connective tissue disorders
    Muscle weakness, generalized or specific area (not due to neuropathy) 11/505 (2.2%) 11 3/504 (0.6%) 3
    Musculoskeletal/Soft Tissue - Other 1/505 (0.2%) 1 2/504 (0.4%) 3
    Osteonecrosis (avascular necrosis) 1/505 (0.2%) 1 1/504 (0.2%) 1
    Trismus (difficulty, restriction or pain when opening mouth) 1/505 (0.2%) 1 0/504 (0%) 0
    Nervous system disorders
    Ataxia (incoordination) 2/505 (0.4%) 2 3/504 (0.6%) 3
    CNS cerebrovascular ischemia 5/505 (1%) 5 2/504 (0.4%) 2
    Cognitive disturbance 1/505 (0.2%) 1 0/504 (0%) 0
    Dizziness 3/505 (0.6%) 3 7/504 (1.4%) 8
    Encephalopathy 2/505 (0.4%) 2 0/504 (0%) 0
    Hemorrhage CNS 0/505 (0%) 0 2/504 (0.4%) 2
    Neurology - Other 1/505 (0.2%) 1 1/504 (0.2%) 1
    Neuropathy: motor 5/505 (1%) 5 4/504 (0.8%) 6
    Neuropathy: sensory 4/505 (0.8%) 4 7/504 (1.4%) 8
    Pain 25/505 (5%) 27 19/504 (3.8%) 24
    Seizure 1/505 (0.2%) 1 1/504 (0.2%) 1
    Somnolence/depressed level of consciousness 3/505 (0.6%) 3 2/504 (0.4%) 3
    Speech impairment (e.g., dysphasia or aphasia) 1/505 (0.2%) 1 0/504 (0%) 0
    Syncope (fainting) 9/505 (1.8%) 10 7/504 (1.4%) 8
    Psychiatric disorders
    Confusion 2/505 (0.4%) 2 5/504 (1%) 5
    Mood alteration 2/505 (0.4%) 2 0/504 (0%) 0
    Psychosis (hallucinations/delusions) 1/505 (0.2%) 1 0/504 (0%) 0
    Renal and urinary disorders
    Bladder spasms 0/505 (0%) 0 1/504 (0.2%) 1
    Cystitis 1/505 (0.2%) 1 1/504 (0.2%) 1
    Fistula, GU 1/505 (0.2%) 1 0/504 (0%) 0
    Hematuria (in the absence of vaginal bleeding) 0/505 (0%) 0 2/504 (0.4%) 2
    Hemoglobinuria 1/505 (0.2%) 1 0/504 (0%) 0
    Hemorrhage GU 6/505 (1.2%) 7 9/504 (1.8%) 10
    Incontinence, urinary 1/505 (0.2%) 1 0/504 (0%) 0
    Obstruction, GU 1/505 (0.2%) 1 5/504 (1%) 5
    Perforation GU 0/505 (0%) 0 1/504 (0.2%) 1
    Proteinuria 22/505 (4.4%) 26 19/504 (3.8%) 21
    Renal failure 3/505 (0.6%) 4 5/504 (1%) 6
    Stricture/stenosis (including anastomotic), GU 0/505 (0%) 0 1/504 (0.2%) 1
    Urinary retention (including neurogenic bladder) 3/505 (0.6%) 3 0/504 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult Respiratory Distress Syndrome (ARDS) 1/505 (0.2%) 1 0/504 (0%) 0
    Aspiration 2/505 (0.4%) 2 0/504 (0%) 0
    Bronchospasm wheezing 1/505 (0.2%) 1 0/504 (0%) 0
    Cough 3/505 (0.6%) 4 0/504 (0%) 0
    Dyspnea (shortness of breath) 15/505 (3%) 18 12/504 (2.4%) 13
    Hemorrhage pulmonary/upper respiratory 23/505 (4.6%) 23 5/504 (1%) 5
    Hypoxia 5/505 (1%) 5 2/504 (0.4%) 2
    Pleural effusion (non-malignant) 2/505 (0.4%) 2 1/504 (0.2%) 1
    Pneumonitis/pulmonary infiltrates 10/505 (2%) 12 3/504 (0.6%) 3
    Pulmonary/Upper Respiratory - Other 1/505 (0.2%) 1 0/504 (0%) 0
    Voice changes/dysarthria (e.g. hoarseness loss or alteration in voice laryngitis) 2/505 (0.4%) 2 0/504 (0%) 0
    Skin and subcutaneous tissue disorders
    Hair loss/alopecia (scalp or body) 0/505 (0%) 0 1/504 (0.2%) 1
    Rash/desquamation 7/505 (1.4%) 8 10/504 (2%) 15
    Rash: hand-foot skin reaction 2/505 (0.4%) 2 0/504 (0%) 0
    Skin breakdown/decubitus ulcer 1/505 (0.2%) 1 0/504 (0%) 0
    Ulceration 0/505 (0%) 0 1/504 (0.2%) 1
    Urticaria (hives welts wheals) 1/505 (0.2%) 1 0/504 (0%) 0
    Vascular disorders
    Hot flashes/flushes 0/505 (0%) 0 1/504 (0.2%) 1
    Hypertension 24/505 (4.8%) 27 6/504 (1.2%) 9
    Hypotension 11/505 (2.2%) 11 6/504 (1.2%) 7
    Thrombosis/thrombus/embolism 17/505 (3.4%) 17 28/504 (5.6%) 31
    Vascular - Other 0/505 (0%) 0 1/504 (0.2%) 1
    Other (Not Including Serious) Adverse Events
    Docetaxel + Placebo Docetaxel + Bevacizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 420/505 (83.2%) 363/504 (72%)
    Blood and lymphatic system disorders
    Febrile neutropenia 15/505 (3%) 15 5/504 (1%) 5
    Hemoglobin 12/505 (2.4%) 20 9/504 (1.8%) 11
    Hemolysis (e.g. immune hemolytic anemia drug-related hemolysis) 0/505 (0%) 0 2/504 (0.4%) 2
    Lymphatics - Other 0/505 (0%) 0 2/504 (0.4%) 2
    Cardiac disorders
    Cardiac Arrhythmia - Other 1/505 (0.2%) 1 0/504 (0%) 0
    Cardiac General - Other 1/505 (0.2%) 1 1/504 (0.2%) 1
    Cardiac ischemia/infarction 4/505 (0.8%) 4 3/504 (0.6%) 3
    Edema 0/505 (0%) 0 1/504 (0.2%) 2
    Supraventricular and nodal arrhythmia 2/505 (0.4%) 3 2/504 (0.4%) 2
    Ear and labyrinth disorders
    Hearing: patients without baseline audiogram and not enrolled in a monitoring program 0/505 (0%) 0 2/504 (0.4%) 2
    Otitis middle ear (non-infectious) 0/505 (0%) 0 1/504 (0.2%) 1
    Eye disorders
    Cataract 2/505 (0.4%) 2 2/504 (0.4%) 2
    Vision-blurred vision 1/505 (0.2%) 1 3/504 (0.6%) 8
    Watery eye (epiphora tearing) 10/505 (2%) 23 2/504 (0.4%) 10
    Gastrointestinal disorders
    Constipation 7/505 (1.4%) 8 2/504 (0.4%) 2
    Dental: periodontal disease 1/505 (0.2%) 2 0/504 (0%) 0
    Diarrhea 18/505 (3.6%) 19 7/504 (1.4%) 9
    Dry mouth/salivary gland (xerostomia) 1/505 (0.2%) 2 0/504 (0%) 0
    Dysphagia (difficulty swallowing) 1/505 (0.2%) 6 0/504 (0%) 0
    Esophagitis 1/505 (0.2%) 1 0/504 (0%) 0
    Fistula, GI 1/505 (0.2%) 1 0/504 (0%) 0
    Gastrointestinal - Other 1/505 (0.2%) 2 0/504 (0%) 0
    Heartburn/dyspepsia 1/505 (0.2%) 1 0/504 (0%) 0
    Hemorrhage, GI 33/505 (6.5%) 46 13/504 (2.6%) 19
    Hemorrhoids 2/505 (0.4%) 2 0/504 (0%) 0
    Ileus GI (functional obstruction of bowel i.e. neuroconstipation) 1/505 (0.2%) 1 0/504 (0%) 0
    Incontinence anal 0/505 (0%) 0 1/504 (0.2%) 1
    Mucositis/stomatitis (clinical exam) 6/505 (1.2%) 7 0/504 (0%) 0
    Mucositis/stomatitis (functional/symptomatic) 12/505 (2.4%) 20 2/504 (0.4%) 2
    Nausea 8/505 (1.6%) 13 7/504 (1.4%) 7
    Perforation, GI 1/505 (0.2%) 1 0/504 (0%) 0
    Rectal bleeding/hematochezia 2/505 (0.4%) 11 0/504 (0%) 0
    Ulcer, GI 1/505 (0.2%) 1 0/504 (0%) 0
    Vomiting 3/505 (0.6%) 4 4/504 (0.8%) 4
    General disorders
    Death not associated with CTCAE term 1/505 (0.2%) 1 2/504 (0.4%) 2
    Edema: limb 1/505 (0.2%) 1 5/504 (1%) 8
    Edema: trunk/genital 0/505 (0%) 0 1/504 (0.2%) 5
    Extremity-lower (gait/walking) 1/505 (0.2%) 1 0/504 (0%) 0
    Fatigue (asthenia, lethargy, malaise) 90/505 (17.8%) 157 51/504 (10.1%) 80
    Fever 77/505 (15.2%) 105 50/504 (9.9%) 64
    Pain - Other 4/505 (0.8%) 4 6/504 (1.2%) 8
    Rigors/chills 42/505 (8.3%) 73 33/504 (6.5%) 67
    Syndromes - Other 1/505 (0.2%) 1 0/504 (0%) 0
    Immune system disorders
    Allergic reaction/hypersensitivity (including drug fever) 20/505 (4%) 56 26/504 (5.2%) 47
    Infections and infestations
    Colitis, infectious (e.g., Clostridium difficile) 1/505 (0.2%) 1 0/504 (0%) 0
    Infection 29/505 (5.7%) 40 15/504 (3%) 18
    Infection - Other 12/505 (2.4%) 23 6/504 (1.2%) 6
    Infection with normal ANC or Grade 1 or 2 neutrophils 36/505 (7.1%) 61 21/504 (4.2%) 28
    Infection with unknown ANC 25/505 (5%) 33 10/504 (2%) 14
    Infection without neutropenia 0/505 (0%) 0 2/504 (0.4%) 2
    Injury, poisoning and procedural complications
    Fracture 0/505 (0%) 0 1/504 (0.2%) 1
    Vessel injury-artery 1/505 (0.2%) 1 0/504 (0%) 0
    Investigations
    ALT, SGPT (serum glutamic pyruvic transaminase) 3/505 (0.6%) 6 0/504 (0%) 0
    AST, SGOT(serum glutamic oxaloacetic transaminase) 2/505 (0.4%) 3 2/504 (0.4%) 2
    Alkaline phosphatase 12/505 (2.4%) 18 12/504 (2.4%) 29
    CD4 count 1/505 (0.2%) 4 0/504 (0%) 0
    Cholesterol serum-high (hypercholesteremia) 1/505 (0.2%) 4 0/504 (0%) 0
    Creatinine 0/505 (0%) 0 1/504 (0.2%) 1
    GGT (gamma-Glutamyl transpeptidase) 2/505 (0.4%) 5 0/504 (0%) 0
    INR (International Normalized Ratio of prothrombin time) 0/505 (0%) 0 3/504 (0.6%) 3
    Leukocytes (total WBC) 56/505 (11.1%) 176 50/504 (9.9%) 113
    Lymphopenia 18/505 (3.6%) 87 31/504 (6.2%) 90
    Metabolic/Laboratory - Other 4/505 (0.8%) 12 1/504 (0.2%) 1
    Neutrophils/granulocytes (ANC/AGC) 110/505 (21.8%) 312 97/504 (19.2%) 252
    PTT (Partial Thromboplastin Time) 1/505 (0.2%) 1 1/504 (0.2%) 1
    Platelets 2/505 (0.4%) 6 0/504 (0%) 0
    Weight gain 0/505 (0%) 0 2/504 (0.4%) 19
    Weight loss 5/505 (1%) 10 2/504 (0.4%) 2
    Metabolism and nutrition disorders
    Albumin, serum-low (hypoalbuminemia) 4/505 (0.8%) 15 0/504 (0%) 0
    Anorexia 14/505 (2.8%) 24 5/504 (1%) 7
    Calcium serum-low (hypocalcemia) 2/505 (0.4%) 2 1/504 (0.2%) 3
    Dehydration 6/505 (1.2%) 6 4/504 (0.8%) 4
    Glucose serum-high (hyperglycemia) 48/505 (9.5%) 142 40/504 (7.9%) 82
    Magnesium serum-low (hypomagnesemia) 0/505 (0%) 0 1/504 (0.2%) 2
    Pancreatic endocrine: glucose intolerance 1/505 (0.2%) 2 1/504 (0.2%) 1
    Phosphate serum-low (hypophosphatemia) 3/505 (0.6%) 5 2/504 (0.4%) 2
    Potassium serum-high (hyperkalemia) 0/505 (0%) 0 1/504 (0.2%) 3
    Potassium serum-low (hypokalemia) 3/505 (0.6%) 6 1/504 (0.2%) 2
    Sodium serum-low (hyponatremia) 9/505 (1.8%) 13 3/504 (0.6%) 5
    Musculoskeletal and connective tissue disorders
    Arthritis (non-septic) 0/505 (0%) 0 1/504 (0.2%) 1
    Muscle weakness, generalized or specific area (not due to neuropathy) 7/505 (1.4%) 13 10/504 (2%) 11
    Musculoskeletal/Soft Tissue - Other 0/505 (0%) 0 1/504 (0.2%) 1
    Osteonecrosis (avascular necrosis) 4/505 (0.8%) 4 1/504 (0.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Secondary Malignancy - possibly related to cancer treatment 0/505 (0%) 0 1/504 (0.2%) 1
    Nervous system disorders
    Ataxia (incoordination) 2/505 (0.4%) 3 0/504 (0%) 0
    CNS cerebrovascular ischemia 2/505 (0.4%) 2 2/504 (0.4%) 2
    Cognitive disturbance 1/505 (0.2%) 1 0/504 (0%) 0
    Dizziness 3/505 (0.6%) 5 2/504 (0.4%) 2
    Encephalopathy 1/505 (0.2%) 1 0/504 (0%) 0
    Extrapyramidal/involuntary movement/restlessness 1/505 (0.2%) 1 0/504 (0%) 0
    Hemorrhage CNS 1/505 (0.2%) 2 1/504 (0.2%) 1
    Neurology - Other 1/505 (0.2%) 1 0/504 (0%) 0
    Neuropathy: cranial 1/505 (0.2%) 1 0/504 (0%) 0
    Neuropathy: motor 9/505 (1.8%) 14 17/504 (3.4%) 32
    Neuropathy: sensory 33/505 (6.5%) 50 33/504 (6.5%) 67
    Pain 44/505 (8.7%) 64 34/504 (6.7%) 43
    Pyramidal tract dysfunction 1/505 (0.2%) 1 0/504 (0%) 0
    Syncope (fainting) 5/505 (1%) 6 5/504 (1%) 7
    Taste alteration (dysgeusia) 3/505 (0.6%) 10 1/504 (0.2%) 1
    Vasovagal episode 1/505 (0.2%) 1 0/504 (0%) 0
    Psychiatric disorders
    Insomnia 2/505 (0.4%) 2 2/504 (0.4%) 2
    Mood alteration 3/505 (0.6%) 6 1/504 (0.2%) 1
    Personality/behavioral 1/505 (0.2%) 1 0/504 (0%) 0
    Renal and urinary disorders
    Bladder spasms 2/505 (0.4%) 2 0/504 (0%) 0
    Cystitis 1/505 (0.2%) 1 0/504 (0%) 0
    Fistula, GU 1/505 (0.2%) 1 0/504 (0%) 0
    Hematuria (in the absence of vaginal bleeding) 0/505 (0%) 0 1/504 (0.2%) 1
    Hemoglobinuria 0/505 (0%) 0 1/504 (0.2%) 2
    Hemorrhage GU 2/505 (0.4%) 4 6/504 (1.2%) 8
    Incontinence, urinary 3/505 (0.6%) 13 3/504 (0.6%) 4
    Obstruction, GU 0/505 (0%) 0 1/504 (0.2%) 1
    Proteinuria 89/505 (17.6%) 295 70/504 (13.9%) 174
    Renal/Genitourinary - Other 1/505 (0.2%) 1 0/504 (0%) 0
    Stricture/stenosis (including anastomotic), GU 0/505 (0%) 0 1/504 (0.2%) 1
    Urinary frequency/urgency 2/505 (0.4%) 2 4/504 (0.8%) 4
    Urinary retention (including neurogenic bladder) 5/505 (1%) 12 4/504 (0.8%) 8
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis (including sneezing nasal stuffiness postnasal drip) 1/505 (0.2%) 2 0/504 (0%) 0
    Cough 3/505 (0.6%) 7 1/504 (0.2%) 1
    Dyspnea (shortness of breath) 8/505 (1.6%) 12 7/504 (1.4%) 7
    Hemorrhage pulmonary/upper respiratory 153/505 (30.3%) 603 54/504 (10.7%) 123
    Hypoxia 0/505 (0%) 0 1/504 (0.2%) 1
    Nasal cavity/paranasal sinus reactions 2/505 (0.4%) 3 0/504 (0%) 0
    Pneumonitis/pulmonary infiltrates 3/505 (0.6%) 3 1/504 (0.2%) 2
    Pulmonary/Upper Respiratory - Other 2/505 (0.4%) 2 0/504 (0%) 0
    Voice changes/dysarthria (e.g. hoarseness loss or alteration in voice laryngitis) 6/505 (1.2%) 11 0/504 (0%) 0
    Skin and subcutaneous tissue disorders
    Dermatology/Skin - Other 2/505 (0.4%) 2 0/504 (0%) 0
    Dry skin 2/505 (0.4%) 2 0/504 (0%) 0
    Hair loss/alopecia (scalp or body) 7/505 (1.4%) 17 5/504 (1%) 12
    Nail changes 8/505 (1.6%) 17 5/504 (1%) 7
    Photosensitivity 2/505 (0.4%) 2 0/504 (0%) 0
    Rash/desquamation 69/505 (13.7%) 155 56/504 (11.1%) 119
    Rash: hand-foot skin reaction 2/505 (0.4%) 11 1/504 (0.2%) 1
    Sweating (diaphoresis) 2/505 (0.4%) 2 0/504 (0%) 0
    Ulceration 1/505 (0.2%) 1 0/504 (0%) 0
    Urticaria (hives welts wheals) 10/505 (2%) 15 4/504 (0.8%) 8
    Vascular disorders
    Dermal change lymphedema phlebolymphedema 1/505 (0.2%) 1 0/504 (0%) 0
    Flushing 1/505 (0.2%) 1 0/504 (0%) 0
    Hemorrhage/Bleeding - Other 0/505 (0%) 0 2/504 (0.4%) 2
    Hot flashes/flushes 4/505 (0.8%) 6 0/504 (0%) 0
    Hypertension 156/505 (30.9%) 568 82/504 (16.3%) 198
    Hypotension 3/505 (0.6%) 3 1/504 (0.2%) 1
    Thrombosis/thrombus/embolism 7/505 (1.4%) 12 20/504 (4%) 61

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title William Kevin Kelly, DO
    Organization Thomas Jefferson University
    Phone
    Email wm.kevin.kelly@jefferson.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00110214
    Other Study ID Numbers:
    • NCI-2012-02814
    • NCI-2012-02814
    • CDR0000427290
    • CALGB-90401
    • CALGB-90401
    • P30CA014236
    • U10CA031946
    First Posted:
    May 5, 2005
    Last Update Posted:
    May 9, 2014
    Last Verified:
    Dec 1, 2012