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S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy

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ClinicalTrials.gov Identifier: NCT00134056
Recruitment Status : Completed
First Posted : August 24, 2005
Results First Posted : May 2, 2017
Last Update Posted : June 2, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Metastatic Cancer
Prostate Cancer
Interventions Drug: atrasentan hydrochloride
Drug: docetaxel
Drug: prednisone
Other: placebo
Enrollment 1038

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Period Title: Randomization
Started 518 520
Completed 496 500
Not Completed 22 20
Reason Not Completed
Not eligible for assigned treatment             22             20
Period Title: Eligible for Protocol Assigned Treatment
Started 496 500
Completed 169 185
Not Completed 327 315
Reason Not Completed
Lack of Efficacy             171             171
Adverse Event             81             67
Withdrawal by Subject             20             21
Not specified             55             56
Arm/Group Title Arm I: Placebo Arm II: Atrasentan Total
Hide Arm/Group Description

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Total of all reporting groups
Overall Number of Baseline Participants 496 498 994
Hide Baseline Analysis Population Description
A total of 1038 patients were randomized to this study, 42 of which were ineligible. Baseline analysis population includes 994 patients (excluding the 42 ineligible patients and 2 additional patients who withdrew all consent prior to receiving protocol treatment).
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 496 participants 498 participants 994 participants
69
(43 to 89)
69
(40 to 92)
69
(40 to 92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
496
 100.0%
498
 100.0%
994
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
Hispanic or Latino
20
   4.0%
21
   4.2%
41
   4.1%
Not Hispanic or Latino
476
  96.0%
477
  95.8%
953
  95.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
White
403
  81.3%
403
  80.9%
806
  81.1%
Black
64
  12.9%
73
  14.7%
137
  13.8%
Asian
12
   2.4%
8
   1.6%
20
   2.0%
Unknown
14
   2.8%
10
   2.0%
24
   2.4%
Serum PSA  
Median (Inter-Quartile Range)
Unit of measure:  ug/L
Number Analyzed 496 participants 498 participants 994 participants
67.7
(24.6 to 202.4)
79.0
(23.5 to 228.3)
72.7
(24.4 to 213.8)
Type of Progression at study entry  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
Measurable or evaluable
394
  79.4%
407
  81.7%
801
  80.6%
PSA increase only
102
  20.6%
91
  18.3%
193
  19.4%
Bisphosphonate use at study entry  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
305
  61.5%
304
  61.0%
609
  61.3%
Brief Pain Inventory, worst pain   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
>= 4
213
  42.9%
210
  42.2%
423
  42.6%
<4
283
  57.1%
288
  57.8%
571
  57.4%
[1]
Measure Description: score >=4 vs <4 in the Brief Pain Inventory scale for worst pain
Metastases  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
Skeletal only
206
  41.5%
203
  40.8%
409
  41.1%
Lymph nodes
148
  29.8%
149
  29.9%
297
  29.9%
Lung, liver or brain
94
  19.0%
101
  20.3%
195
  19.6%
Extraskeletal
48
   9.7%
45
   9.0%
93
   9.4%
Previous prostatectomy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
145
  29.2%
168
  33.7%
313
  31.5%
Performance status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
2-3
39
   7.9%
36
   7.2%
75
   7.5%
0-1
457
  92.1%
462
  92.8%
919
  92.5%
[1]
Measure Description:

SWOG Performance status:

0 = Fully active, able to carry on all pre-disease performance without restriction.

  1. = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
  2. = Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.
  3. = Capable of limited self-care, confined to bed or chair more than 50% of waking hours.
Gleason score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
5-6
49
   9.9%
52
  10.4%
101
  10.2%
7
137
  27.6%
141
  28.3%
278
  28.0%
8-10
272
  54.8%
275
  55.2%
547
  55.0%
Missing
38
   7.7%
30
   6.0%
68
   6.8%
[1]
Measure Description:

Pathologists grade prostate cancers using numbers from 1 to 5 based on how much the cells in the cancerous tissue look like normal tissue. This is called the Gleason system.

If the cancerous tissue looks like normal tissue, a grade of 1 is assigned. If the cancer cells look very abnormal, a grade of 5 is assigned. Grades 2-4 have features in between these extremes.

Since prostate cancers often have areas with different grades, a grade is assigned to the 2 areas that make up most of the cancer. These 2 grades are added to yield the Gleason score. The highest a Gleason score can be is 10.

1.Primary Outcome
Title Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.
Hide Description Measured from date of registration to date of death due to any cause. Patient last known to be alive are censored at date of last contact.
Time Frame Up to 7 years after study opens
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description:

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Overall Number of Participants Analyzed 496 498
Median (95% Confidence Interval)
Unit of Measure: months
17.6
(16.4 to 20.1)
17.8
(16.4 to 19.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I: Placebo, Arm II: Atrasentan
Comments The primary analysis was by intention to treat and the Hochberg procedure was used for multiple testing of co-primary endpoints. Assuming a 4 year accrual, 2.5 years of follow-up, and 930 eligible patients, the study was designed to have 87% power to detect a 25% increase from 18.0 months to 22.5 months in median overall survival with a one-sided log rank with alpha of 0.0125.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.90 to 1.19
Estimation Comments [Not Specified]
2.Primary Outcome
Title Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.
Hide Description Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients without progression are censored at date of last contact. Disease progression is defined by confirmed bone disease progression, soft tissue or pain progression.
Time Frame Up to 7 years after study opens
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description:

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Overall Number of Participants Analyzed 496 498
Median (95% Confidence Interval)
Unit of Measure: months
9.1
(8.4 to 10.2)
9.2
(8.5 to 9.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I: Placebo, Arm II: Atrasentan
Comments The primary analysis was by intention to treat and the Hochberg procedure was used for multiple testing of co-primary endpoints. Assuming a 4 year accrual, 2.5 years of follow-up, and 930 eligible patients, the study was designed to have 87% power to detect a 25% increase from 6.0 months to 7.5 months in median overall survival with a one-sided log rank with alpha of 0.0125.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.89 to 1.16
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Compare Pain Progression Between the Two Study Arms.
Hide Description Pain progression is defined as patients reporting an increase of at least two Worst Pain points, maintained for at least two consecutive assessments, increase to Level 3 (strong opioid) on the Pain Medication Log Analgesic Code for patients receiving Level 2 (weak opioid) analgesics at randomization, or an increase to Level 2 or 3 analgesics for patients receiving Level 0 or 1 analgesics at randomization.
Time Frame Up to 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only those patients who progressed on study were included in this analysis. The proportion of patients with pain progression is calculated using number of patients with pain progression as the numerator and the total number of patients who progressed on study as the denominator.
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description:

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Overall Number of Participants Analyzed 416 408
Measure Type: Count of Participants
Unit of Measure: Participants
59
  14.2%
41
  10.0%
4.Secondary Outcome
Title Compare Qualitative and Quantitative Toxicity Between the Two Study Arms
Hide Description Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame Assessed every 3 weeks up to 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
patients with hormone-refractory stage IV prostate cancer and bone metastases treated with docetaxel and prednisone combined with either atrasentan vs placebo
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description:
Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.
Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
Overall Number of Participants Analyzed 486 492
Measure Type: Number
Unit of Measure: Participants
ALT, SGPT (serum glutamic pyruvic transaminase) 2 2
AST, SGOT 2 4
Adult respiratory distress syndrome (ARDS) 3 0
Albumin, serum-low (hypoalbuminemia) 3 0
Alkaline phosphatase 4 6
Allergic reaction/hypersensitivity 5 6
Allergy/Immunology-Other (Specify) 0 1
Amylase 0 1
Anorexia 5 5
Arthritis (non-septic) 1 0
Aspiration 0 1
Auditory/Ear-Other (Specify) 1 0
Bilirubin (hyperbilirubinemia) 0 1
Blood/Bone Marrow-Other (Specify) 2 2
CNS cerebrovascular ischemia 0 1
CPK (creatine phosphokinase) 2 0
Calcium, serum-low (hypocalcemia) 7 1
Cardiac Arrhythmia-Other (Specify) 2 0
Cardiac General-Other (Specify) 1 1
Cardiac troponin I (cTnI) 2 1
Cardiac troponin T (cTnT) 1 0
Cardiac-ischemia/infarction 2 1
Conduction abnormality NOS 1 0
Confusion 1 0
Constipation 3 4
Cough 1 2
Creatinine 4 1
Dehydration 9 8
Diarrhea 10 7
Dizziness 3 1
Dry mouth/salivary gland (xerostomia) 1 0
Dysphagia (difficulty swallowing) 1 1
Dyspnea (shortness of breath) 38 17
Edema: head and neck 0 1
Edema: limb 16 2
Edema: trunk/genital 1 0
Erectile dysfunction 2 0
Esophagitis 0 1
Fatigue (asthenia, lethargy, malaise) 60 40
Febrile neutropenia 8 20
Fever in absence of neutropenia, ANC lt1.0x10e9/L 1 2
Fracture 1 0
Glucose, serum-high (hyperglycemia) 20 24
Glucose, serum-low (hypoglycemia) 1 0
Heartburn/dyspepsia 1 1
Hemoglobin 47 22
Hemolysis 1 0
Hemorrhage, Respiratory tract NOS 0 1
Hemorrhage, GI - Rectum 1 0
Hemorrhage, GI - Stomach 1 0
Hemorrhage, GI - Upper GI NOS 0 1
Hemorrhage, GU - Bladder 0 1
Hemorrhage/Bleeding-Other (Specify) 2 1
Hemorrhoids 0 2
Hot flashes/flushes 2 1
Hypertension 2 2
Hypotension 9 3
Hypoxia 10 3
INR (of prothrombin time) 3 1
Induration/fibrosis (skin and subcutaneous tissue) 1 0
Inf (clin/microbio) w/Gr 3-4 neuts - Bladder 1 2
Inf (clin/microbio) w/Gr 3-4 neuts - Blood 2 0
Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus 0 1
Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus 0 1
Inf (clin/microbio) w/Gr 3-4 neuts - Lung 11 6
Inf (clin/microbio) w/Gr 3-4 neuts - Nerve-periph 1 0
Inf (clin/microbio) w/Gr 3-4 neuts - Skin 1 2
Inf (clin/microbio) w/Gr 3-4 neuts - Soft tissue 1 0
Inf (clin/microbio) w/Gr 3-4 neuts - UTI 4 3
Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway 0 2
Inf w/normal ANC or Gr 1-2 neutrophils - Blood 2 1
Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus 1 1
Inf w/normal ANC or Gr 1-2 neutrophils - Colon 1 0
Inf w/normal ANC or Gr 1-2 neutrophils - Lung 1 5
Inf w/normal ANC or Gr 1-2 neutrophils - Muscle 1 0
Inf w/normal ANC or Gr 1-2 neutrophils - Scrotum 0 1
Inf w/normal ANC or Gr 1-2 neutrophils - Sinus 1 0
Inf w/normal ANC or Gr 1-2 neutrophils - Skin 1 2
Inf w/normal ANC or Gr 1-2 neutrophils - Stomach 1 0
Inf w/normal ANC or Gr 1-2 neutrophils - Trachea 1 0
Inf w/normal ANC or Gr 1-2 neutrophils - UTI 0 1
Inf w/normal ANC or Gr 1-2 neutrophils - Ungual 0 1
Inf w/unknown ANC - Middle ear (otitis media) 0 1
Inf w/unknown ANC - Upper aerodigestive NOS 0 1
Infection with unknown ANC - Blood 0 1
Infection with unknown ANC - Lung (pneumonia) 3 0
Infection with unknown ANC - Upper airway NOS 0 1
Infection with unknown ANC - Urinary tract NOS 1 1
Infection-Other (Specify) 4 3
Insomnia 1 1
Left ventricular diastolic dysfunction 1 0
Left ventricular systolic dysfunction 3 2
Leukocytes (total WBC) 101 98
Lipase 0 1
Lymphopenia 30 32
Magnesium, serum-high (hypermagnesemia) 1 0
Metabolic/Laboratory-Other (Specify) 0 2
Mood alteration - agitation 1 0
Mood alteration - depression 1 0
Mucositis/stomatitis (clinical exam) - Oral cavity 2 2
Mucositis/stomatitis (clinical exam) - Pharynx 1 0
Mucositis/stomatitis (clinical exam) - Stomach 1 0
Mucositis/stomatitis (functional/symp) - Esophagus 0 1
Mucositis/stomatitis (functional/symp) - Oral cav 3 3
Mucositis/stomatitis (functional/symp) - Pharynx 0 1
Mucositis/stomatitis (functional/symp) - Rectum 0 1
Muscle weakness, not d/t neuropathy - Extrem-lower 2 1
Muscle weakness, not d/t neuropathy - body/general 11 8
Myocarditis 1 0
Nail changes 0 1
Nasal cavity/paranasal sinus reactions 2 0
Nausea 11 5
Neuropathy: motor 7 6
Neuropathy: sensory 10 11
Neutrophils/granulocytes (ANC/AGC) 140 154
Opportunistic inf associated w/gt=Gr 2 lymphopenia 1 1
PTT (Partial thromboplastin time) 1 0
Pain - Abdomen NOS 4 0
Pain - Back 1 2
Pain - Bone 5 8
Pain - Chest wall 0 1
Pain - Chest/thorax NOS 1 0
Pain - Extremity-limb 1 1
Pain - Joint 2 2
Pain - Muscle 8 3
Pain - Neuralgia/peripheral nerve 1 1
Pain - Pelvis 0 1
Pain-Other (Specify) 0 1
Phosphate, serum-low (hypophosphatemia) 3 0
Platelets 7 4
Pneumonitis/pulmonary infiltrates 7 0
Pneumothorax 1 0
Potassium, serum-high (hyperkalemia) 2 1
Potassium, serum-low (hypokalemia) 11 2
Pulmonary/Upper Respiratory-Other (Specify) 0 1
Rash: hand-foot skin reaction 1 0
Renal failure 4 2
Renal/Genitourinary-Other (Specify) 1 0
Right ventricular dysfunction (cor pulmonale) 0 1
SVT and nodal arrhythmia - Atrial fibrillation 3 2
SVT and nodal arrhythmia - Atrial flutter 1 1
SVT and nodal arrhythmia - Sinus tachycardia 0 1
Sodium, serum-low (hyponatremia) 8 3
Somnolence/depressed level of consciousness 1 0
Speech impairment (e.g., dysphasia or aphasia) 0 1
Sudden death 2 0
Syncope (fainting) 3 1
Thrombosis/embolism (vascular access-related) 0 1
Thrombosis/thrombus/embolism 9 11
Vasovagal episode 0 2
Vomiting 8 7
Watery eye (epiphora, tearing) 0 1
Weight gain 0 1
5.Secondary Outcome
Title Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm.
Hide Description PSA Partial Response: Greater than or equal to 50% reduction in baseline PSA. There must be no evidence of soft tissue progression, or confirmed none disease progression, or pain progression.
Time Frame Up to 7 years after study opens
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description:

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Overall Number of Participants Analyzed 496 498
Measure Type: Count of Participants
Unit of Measure: Participants
243
  49.0%
249
  50.0%
6.Secondary Outcome
Title Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria.
Hide Description Complete Response (CR): Complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. PSA ≤ .2 ng/ml. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.
Time Frame Up to 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
450 (225 in each arm) of 461 patients with measurable disease at trial enrollment were assessable for response by RECIST.
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description:

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Overall Number of Participants Analyzed 225 225
Measure Type: Count of Participants
Unit of Measure: Participants
Partial response (confirmed)
31
  13.8%
32
  14.2%
Complete response
0
   0.0%
0
   0.0%
No response
194
  86.2%
193
  85.8%
7.Other Pre-specified Outcome
Title Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI)
Hide Description Pain palliation is the proportion of patients showing a two-point reduction in the Worst Pain score (WPS) maintained for two consecutive assessments with no increase in analgesic use. Increase in analgesic use is defined as an increase in Analgesic code Level to 2 (weak opioid) or 3 (strong opioid). Patients will be classified as pain palliated or not palliated. Patients with a WPS of "0" will be defined as "stable" if their WPS remains "0" for Weeks 7 and 10 with no increase in analgesic use, but they will not be categorized as responders. Pain palliation response is measured by BPI short form that has the following: yes/no question about pain today; 4 pain rating questions (worst pain, least pain, average pain, and current pain); pain medications and pain relief; 7 items addressing effect of pain on functioning. For patients who continue to receive treatment beyond 12 treatment cycles, the Worst Pain item is measured by Pain Medication Log and Pain Assessment
Time Frame up to 18 months study period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
There was a large amount of missing data points due to the difficulty of data collection of pain medication logs in addition to a questionnaire.The study team and site staff were only able to obtain complete data for the patients included in this analysis.
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description:

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Overall Number of Participants Analyzed 274 260
Measure Type: Count of Participants
Unit of Measure: Participants
75
  27.4%
83
  31.9%
8.Other Pre-specified Outcome
Title Number of Patients With a Change in Functional Status
Hide Description Functional status will be measured with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index. The FACT-P also addresses four general domains of QOL (physical, functional, emotional, and social well-being subscales) as well as symptom concerns associated with prostate cancer and its treatment.
Time Frame up to 18 months study period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Placebo Arm II: Atrasentan Hydrochloride
Hide Arm/Group Description:

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Overall Number of Participants Analyzed 487 484
Measure Type: Count of Participants
Unit of Measure: Participants
118
  24.2%
139
  28.7%
Time Frame Assessed every 3 weeks up to 52 weeks
Adverse Event Reporting Description Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
 
Arm/Group Title Arm I: Placebo Arm II: Atrasentan
Hide Arm/Group Description Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
All-Cause Mortality
Arm I: Placebo Arm II: Atrasentan
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm I: Placebo Arm II: Atrasentan
Affected / at Risk (%) Affected / at Risk (%)
Total   172/486 (35.39%)   153/492 (31.10%) 
Blood and lymphatic system disorders     
DIC (disseminated intravascular coagulation)  1  1/486 (0.21%)  0/492 (0.00%) 
Febrile neutropenia  1  9/486 (1.85%)  9/492 (1.83%) 
Hemoglobin  1  10/486 (2.06%)  5/492 (1.02%) 
Cardiac disorders     
Cardiac General-Other  1  3/486 (0.62%)  0/492 (0.00%) 
Cardiac-ischemia/infarction  1  7/486 (1.44%)  2/492 (0.41%) 
Cardiopulmonary arrest, cause unknown (non-fatal)  1  0/486 (0.00%)  2/492 (0.41%) 
Left ventricular diastolic dysfunction  1  2/486 (0.41%)  0/492 (0.00%) 
Left ventricular systolic dysfunction  1  1/486 (0.21%)  2/492 (0.41%) 
Myocarditis  1  1/486 (0.21%)  0/492 (0.00%) 
Right ventricular dysfunction (cor pulmonale)  1  0/486 (0.00%)  1/492 (0.20%) 
SVT and nodal arrhythmia - Atrial fibrillation  1  8/486 (1.65%)  3/492 (0.61%) 
SVT and nodal arrhythmia - Atrial flutter  1  3/486 (0.62%)  2/492 (0.41%) 
SVT and nodal arrhythmia - Sinus bradycardia  1  1/486 (0.21%)  0/492 (0.00%) 
Ventricular arrhythmia - PVCs  1  1/486 (0.21%)  0/492 (0.00%) 
Ventricular arrhythmia - Ventricular fibrillation  1  0/486 (0.00%)  1/492 (0.20%) 
Ventricular arrhythmia - Ventricular tachycardia  1  1/486 (0.21%)  0/492 (0.00%) 
Ear and labyrinth disorders     
Otitis, middle ear (non-infectious)  1  1/486 (0.21%)  0/492 (0.00%) 
Eye disorders     
Vision-blurred vision  1  0/486 (0.00%)  1/492 (0.20%) 
Gastrointestinal disorders     
Colitis  1  1/486 (0.21%)  0/492 (0.00%) 
Constipation  1  1/486 (0.21%)  3/492 (0.61%) 
Diarrhea  1  6/486 (1.23%)  4/492 (0.81%) 
Distention/bloating, abdominal  1  1/486 (0.21%)  0/492 (0.00%) 
Dry mouth/salivary gland (xerostomia)  1  1/486 (0.21%)  0/492 (0.00%) 
Dysphagia (difficulty swallowing)  1  1/486 (0.21%)  1/492 (0.20%) 
Esophagitis  1  0/486 (0.00%)  1/492 (0.20%) 
Gastrointestinal-Other  1  1/486 (0.21%)  0/492 (0.00%) 
Hemorrhage, GI - Abdomen NOS  1  1/486 (0.21%)  0/492 (0.00%) 
Hemorrhage, GI - Colon  1  1/486 (0.21%)  1/492 (0.20%) 
Hemorrhage, GI - Duodenum  1  2/486 (0.41%)  2/492 (0.41%) 
Hemorrhage, GI - Lower GI NOS  1  0/486 (0.00%)  1/492 (0.20%) 
Hemorrhage, GI - Rectum  1  3/486 (0.62%)  2/492 (0.41%) 
Hemorrhage, GI - Stomach  1  1/486 (0.21%)  0/492 (0.00%) 
Hemorrhage, GI - Upper GI NOS  1  1/486 (0.21%)  3/492 (0.61%) 
Ileus, GI (functional obstruction of bowel)  1  1/486 (0.21%)  0/492 (0.00%) 
Mucositis/stomatitis (clinical exam) - Esophagus  1  0/486 (0.00%)  1/492 (0.20%) 
Mucositis/stomatitis (clinical exam) - Oral cavity  1  2/486 (0.41%)  1/492 (0.20%) 
Nausea  1  5/486 (1.03%)  6/492 (1.22%) 
Obstruction, GI - Colon  1  0/486 (0.00%)  1/492 (0.20%) 
Obstruction, GI - Small bowel NOS  1  1/486 (0.21%)  3/492 (0.61%) 
Pain - Abdomen NOS  1  7/486 (1.44%)  5/492 (1.02%) 
Perforation, GI - Colon  1  1/486 (0.21%)  0/492 (0.00%) 
Perforation, GI - Duodenum  1  0/486 (0.00%)  1/492 (0.20%) 
Perforation, GI - Small bowel NOS  1  0/486 (0.00%)  1/492 (0.20%) 
Proctitis  1  0/486 (0.00%)  1/492 (0.20%) 
Stricture/stenosis (including anastomotic), GI - A  1  1/486 (0.21%)  0/492 (0.00%) 
Ulcer, GI - Duodenum  1  2/486 (0.41%)  2/492 (0.41%) 
Ulcer, GI - Rectum  1  1/486 (0.21%)  0/492 (0.00%) 
Ulcer, GI - Stomach  1  1/486 (0.21%)  1/492 (0.20%) 
Vomiting  1  6/486 (1.23%)  9/492 (1.83%) 
General disorders     
Death - Multi-organ failure  1  3/486 (0.62%)  0/492 (0.00%) 
Death not associated with CTCAE term - Death NOS  1  4/486 (0.82%)  5/492 (1.02%) 
Edema: head and neck  1  0/486 (0.00%)  1/492 (0.20%) 
Edema: limb  1  4/486 (0.82%)  0/492 (0.00%) 
Fatigue (asthenia, lethargy, malaise)  1  14/486 (2.88%)  6/492 (1.22%) 
Fever in absence of neutropenia, ANC lt1.0x10e9/L  1  0/486 (0.00%)  1/492 (0.20%) 
Pain - Chest/thorax NOS  1  2/486 (0.41%)  2/492 (0.41%) 
Pain - Pain NOS  1  0/486 (0.00%)  1/492 (0.20%) 
Pain-Other  1  3/486 (0.62%)  1/492 (0.20%) 
Sudden death  1  3/486 (0.62%)  2/492 (0.41%) 
Infections and infestations     
Inf (clin/microbio) w/Gr 3-4 neuts - Appendix  1  0/486 (0.00%)  1/492 (0.20%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Bladder  1  1/486 (0.21%)  2/492 (0.41%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Blood  1  4/486 (0.82%)  3/492 (0.61%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Colon  1  1/486 (0.21%)  0/492 (0.00%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Eye NOS  1  1/486 (0.21%)  0/492 (0.00%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Lung  1  14/486 (2.88%)  8/492 (1.63%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Nerve-periph  1  1/486 (0.21%)  0/492 (0.00%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Nose  1  1/486 (0.21%)  0/492 (0.00%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Pharynx  1  1/486 (0.21%)  0/492 (0.00%) 
Inf (clin/microbio) w/Gr 3-4 neuts - UTI  1  7/486 (1.44%)  6/492 (1.22%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway  1  0/486 (0.00%)  1/492 (0.20%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Ab NOS  1  1/486 (0.21%)  0/492 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Bladder  1  0/486 (0.00%)  1/492 (0.20%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Blood  1  5/486 (1.03%)  0/492 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus  1  0/486 (0.00%)  1/492 (0.20%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter  1  2/486 (0.41%)  0/492 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Colon  1  1/486 (0.21%)  0/492 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Liver  1  1/486 (0.21%)  0/492 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Lung  1  12/486 (2.47%)  9/492 (1.83%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Mid ear  1  0/486 (0.00%)  1/492 (0.20%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Muscle  1  1/486 (0.21%)  0/492 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Scrotum  1  0/486 (0.00%)  1/492 (0.20%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Skin  1  3/486 (0.62%)  2/492 (0.41%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Trachea  1  1/486 (0.21%)  0/492 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - UTI  1  3/486 (0.62%)  4/492 (0.81%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Wound  1  0/486 (0.00%)  2/492 (0.41%) 
Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-peri  1  0/486 (0.00%)  1/492 (0.20%) 
Inf w/unknown ANC - Middle ear (otitis media)  1  0/486 (0.00%)  1/492 (0.20%) 
Inf w/unknown ANC - Upper aerodigestive NOS  1  0/486 (0.00%)  1/492 (0.20%) 
Infection (documented clinically or microbiologica  1  2/486 (0.41%)  0/492 (0.00%) 
Infection with unknown ANC - Blood  1  0/486 (0.00%)  1/492 (0.20%) 
Infection with unknown ANC - Lung (pneumonia)  1  1/486 (0.21%)  0/492 (0.00%) 
Infection with unknown ANC - Rectum  1  0/486 (0.00%)  1/492 (0.20%) 
Infection with unknown ANC - Upper airway NOS  1  0/486 (0.00%)  1/492 (0.20%) 
Infection with unknown ANC - Urinary tract NOS  1  0/486 (0.00%)  1/492 (0.20%) 
Infection with unknown ANC - Wound  1  1/486 (0.21%)  0/492 (0.00%) 
Infection-Other  1  1/486 (0.21%)  1/492 (0.20%) 
Perforation, GI - Appendix  1  0/486 (0.00%)  3/492 (0.61%) 
Injury, poisoning and procedural complications     
Fracture  1  5/486 (1.03%)  3/492 (0.61%) 
Thrombosis/embolism (vascular access-related)  1  0/486 (0.00%)  1/492 (0.20%) 
Investigations     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  0/486 (0.00%)  1/492 (0.20%) 
AST, SGOT  1  1/486 (0.21%)  1/492 (0.20%) 
Alkaline phosphatase  1  1/486 (0.21%)  1/492 (0.20%) 
Bilirubin (hyperbilirubinemia)  1  1/486 (0.21%)  0/492 (0.00%) 
CPK (creatine phosphokinase)  1  1/486 (0.21%)  0/492 (0.00%) 
Cardiac troponin I (cTnI)  1  5/486 (1.03%)  1/492 (0.20%) 
Cardiac troponin T (cTnT)  1  1/486 (0.21%)  0/492 (0.00%) 
Creatinine  1  6/486 (1.23%)  4/492 (0.81%) 
Fibrinogen  1  1/486 (0.21%)  0/492 (0.00%) 
INR (of prothrombin time)  1  1/486 (0.21%)  1/492 (0.20%) 
Leukocytes (total WBC)  1  8/486 (1.65%)  8/492 (1.63%) 
Lymphopenia  1  1/486 (0.21%)  1/492 (0.20%) 
Metabolic/Laboratory-Other  1  0/486 (0.00%)  1/492 (0.20%) 
Neutrophils/granulocytes (ANC/AGC)  1  15/486 (3.09%)  11/492 (2.24%) 
Platelets  1  1/486 (0.21%)  0/492 (0.00%) 
Prolonged QTc interval  1  1/486 (0.21%)  0/492 (0.00%) 
Weight loss  1  1/486 (0.21%)  0/492 (0.00%) 
Metabolism and nutrition disorders     
Acidosis (metabolic or respiratory)  1  1/486 (0.21%)  1/492 (0.20%) 
Albumin, serum-low (hypoalbuminemia)  1  2/486 (0.41%)  1/492 (0.20%) 
Anorexia  1  4/486 (0.82%)  4/492 (0.81%) 
Calcium, serum-low (hypocalcemia)  1  7/486 (1.44%)  0/492 (0.00%) 
Dehydration  1  13/486 (2.67%)  7/492 (1.42%) 
Glucose, serum-high (hyperglycemia)  1  5/486 (1.03%)  7/492 (1.42%) 
Glucose, serum-low (hypoglycemia)  1  2/486 (0.41%)  0/492 (0.00%) 
Magnesium, serum-high (hypermagnesemia)  1  1/486 (0.21%)  0/492 (0.00%) 
Phosphate, serum-low (hypophosphatemia)  1  1/486 (0.21%)  0/492 (0.00%) 
Potassium, serum-high (hyperkalemia)  1  0/486 (0.00%)  1/492 (0.20%) 
Potassium, serum-low (hypokalemia)  1  3/486 (0.62%)  0/492 (0.00%) 
Sodium, serum-low (hyponatremia)  1  3/486 (0.62%)  4/492 (0.81%) 
Musculoskeletal and connective tissue disorders     
Joint-effusion  1  1/486 (0.21%)  0/492 (0.00%) 
Muscle weakness, not d/t neuropathy - Extrem-lower  1  2/486 (0.41%)  2/492 (0.41%) 
Muscle weakness, not d/t neuropathy - body/general  1  4/486 (0.82%)  3/492 (0.61%) 
Musculoskeletal/Soft Tissue-Other  1  1/486 (0.21%)  0/492 (0.00%) 
Osteonecrosis (avascular necrosis)  1  0/486 (0.00%)  1/492 (0.20%) 
Pain - Back  1  3/486 (0.62%)  3/492 (0.61%) 
Pain - Bone  1  5/486 (1.03%)  2/492 (0.41%) 
Pain - Chest wall  1  0/486 (0.00%)  1/492 (0.20%) 
Pain - Extremity-limb  1  2/486 (0.41%)  4/492 (0.81%) 
Pain - Joint  1  1/486 (0.21%)  0/492 (0.00%) 
Pain - Muscle  1  1/486 (0.21%)  0/492 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Death - Disease progression NOS  1  10/486 (2.06%)  11/492 (2.24%) 
Pain - Tumor pain  1  1/486 (0.21%)  0/492 (0.00%) 
Nervous system disorders     
CNS cerebrovascular ischemia  1  0/486 (0.00%)  4/492 (0.81%) 
Dizziness  1  1/486 (0.21%)  3/492 (0.61%) 
Hemorrhage, CNS  1  1/486 (0.21%)  1/492 (0.20%) 
Mental status  1  0/486 (0.00%)  1/492 (0.20%) 
Neurology-Other  1  0/486 (0.00%)  1/492 (0.20%) 
Neuropathy: CN III Pupil, eyelid, xtra ocular mvmt  1  0/486 (0.00%)  1/492 (0.20%) 
Neuropathy: CN VII Motor-face; Sensory-taste  1  0/486 (0.00%)  1/492 (0.20%) 
Neuropathy: cranial - CN VI Lateral deviation of e  1  0/486 (0.00%)  1/492 (0.20%) 
Neuropathy: motor  1  1/486 (0.21%)  2/492 (0.41%) 
Pain - Head/headache  1  0/486 (0.00%)  1/492 (0.20%) 
Somnolence/depressed level of consciousness  1  3/486 (0.62%)  0/492 (0.00%) 
Speech impairment (e.g., dysphasia or aphasia)  1  0/486 (0.00%)  1/492 (0.20%) 
Syncope (fainting)  1  4/486 (0.82%)  0/492 (0.00%) 
Taste alteration (dysgeusia)  1  1/486 (0.21%)  0/492 (0.00%) 
Vasovagal episode  1  0/486 (0.00%)  1/492 (0.20%) 
Psychiatric disorders     
Confusion  1  4/486 (0.82%)  4/492 (0.81%) 
Mood alteration - depression  1  0/486 (0.00%)  2/492 (0.41%) 
Personality/behavioral  1  0/486 (0.00%)  1/492 (0.20%) 
Psychosis (hallucinations/delusions)  1  0/486 (0.00%)  1/492 (0.20%) 
Renal and urinary disorders     
Hemorrhage, GU - Bladder  1  0/486 (0.00%)  2/492 (0.41%) 
Hemorrhage, GU - Urinary NOS  1  1/486 (0.21%)  1/492 (0.20%) 
Obstruction, GU - Ureter  1  0/486 (0.00%)  2/492 (0.41%) 
Obstruction, GU - Urethra  1  0/486 (0.00%)  1/492 (0.20%) 
Renal failure  1  8/486 (1.65%)  7/492 (1.42%) 
Renal/Genitourinary-Other  1  1/486 (0.21%)  0/492 (0.00%) 
Urinary retention (including neurogenic bladder)  1  3/486 (0.62%)  3/492 (0.61%) 
Reproductive system and breast disorders     
Pain - Testicle  1  0/486 (0.00%)  1/492 (0.20%) 
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome (ARDS)  1  2/486 (0.41%)  1/492 (0.20%) 
Aspiration  1  0/486 (0.00%)  1/492 (0.20%) 
Dyspnea (shortness of breath)  1  25/486 (5.14%)  9/492 (1.83%) 
Edema, larynx  1  0/486 (0.00%)  1/492 (0.20%) 
Hemorrhage, Respiratory tract NOS  1  0/486 (0.00%)  1/492 (0.20%) 
Hemorrhage, pulmonary/upper respiratory - Lung  1  1/486 (0.21%)  0/492 (0.00%) 
Hypoxia  1  10/486 (2.06%)  3/492 (0.61%) 
Pleural effusion (non-malignant)  1  2/486 (0.41%)  0/492 (0.00%) 
Pneumonitis/pulmonary infiltrates  1  7/486 (1.44%)  4/492 (0.81%) 
Pulmonary fibrosis (radiographic changes)  1  0/486 (0.00%)  1/492 (0.20%) 
Skin and subcutaneous tissue disorders     
Dermatology/Skin-Other  1  0/486 (0.00%)  1/492 (0.20%) 
Hyperpigmentation  1  1/486 (0.21%)  0/492 (0.00%) 
Induration/fibrosis (skin and subcutaneous tissue)  1  1/486 (0.21%)  0/492 (0.00%) 
Pain - Scalp  1  0/486 (0.00%)  1/492 (0.20%) 
Vascular disorders     
Hematoma  1  0/486 (0.00%)  1/492 (0.20%) 
Hypertension  1  2/486 (0.41%)  1/492 (0.20%) 
Hypotension  1  13/486 (2.67%)  7/492 (1.42%) 
Thrombosis/thrombus/embolism  1  12/486 (2.47%)  17/492 (3.46%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I: Placebo Arm II: Atrasentan
Affected / at Risk (%) Affected / at Risk (%)
Total   476/486 (97.94%)   475/492 (96.54%) 
Blood and lymphatic system disorders     
Hemoglobin  1  350/486 (72.02%)  331/492 (67.28%) 
Eye disorders     
Vision-blurred vision  1  26/486 (5.35%)  14/492 (2.85%) 
Watery eye (epiphora, tearing)  1  37/486 (7.61%)  41/492 (8.33%) 
Gastrointestinal disorders     
Constipation  1  185/486 (38.07%)  176/492 (35.77%) 
Diarrhea  1  143/486 (29.42%)  149/492 (30.28%) 
Dry mouth/salivary gland (xerostomia)  1  33/486 (6.79%)  23/492 (4.67%) 
Heartburn/dyspepsia  1  36/486 (7.41%)  43/492 (8.74%) 
Mucositis/stomatitis (clinical exam) - Oral cavity  1  39/486 (8.02%)  27/492 (5.49%) 
Mucositis/stomatitis (functional/symp) - Oral cav  1  30/486 (6.17%)  46/492 (9.35%) 
Nausea  1  201/486 (41.36%)  188/492 (38.21%) 
Pain - Abdomen NOS  1  29/486 (5.97%)  46/492 (9.35%) 
Vomiting  1  78/486 (16.05%)  62/492 (12.60%) 
General disorders     
Edema: limb  1  284/486 (58.44%)  178/492 (36.18%) 
Fatigue (asthenia, lethargy, malaise)  1  357/486 (73.46%)  346/492 (70.33%) 
Fever in absence of neutropenia, ANC lt1.0x10e9/L  1  43/486 (8.85%)  30/492 (6.10%) 
Pain-Other  1  32/486 (6.58%)  34/492 (6.91%) 
Injury, poisoning and procedural complications     
Bruising (in absence of Gr 3-4 thrombocytopenia)  1  27/486 (5.56%)  21/492 (4.27%) 
Investigations     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  33/486 (6.79%)  36/492 (7.32%) 
AST, SGOT  1  71/486 (14.61%)  80/492 (16.26%) 
Alkaline phosphatase  1  106/486 (21.81%)  113/492 (22.97%) 
Creatinine  1  79/486 (16.26%)  71/492 (14.43%) 
Leukocytes (total WBC)  1  165/486 (33.95%)  165/492 (33.54%) 
Lymphopenia  1  76/486 (15.64%)  72/492 (14.63%) 
Metabolic/Laboratory-Other  1  23/486 (4.73%)  27/492 (5.49%) 
Neutrophils/granulocytes (ANC/AGC)  1  179/486 (36.83%)  180/492 (36.59%) 
Platelets  1  71/486 (14.61%)  47/492 (9.55%) 
Weight gain  1  49/486 (10.08%)  36/492 (7.32%) 
Weight loss  1  39/486 (8.02%)  36/492 (7.32%) 
Metabolism and nutrition disorders     
Albumin, serum-low (hypoalbuminemia)  1  91/486 (18.72%)  90/492 (18.29%) 
Anorexia  1  112/486 (23.05%)  106/492 (21.54%) 
Calcium, serum-low (hypocalcemia)  1  109/486 (22.43%)  75/492 (15.24%) 
Dehydration  1  27/486 (5.56%)  29/492 (5.89%) 
Glucose, serum-high (hyperglycemia)  1  191/486 (39.30%)  202/492 (41.06%) 
Potassium, serum-high (hyperkalemia)  1  36/486 (7.41%)  33/492 (6.71%) 
Potassium, serum-low (hypokalemia)  1  59/486 (12.14%)  47/492 (9.55%) 
Sodium, serum-low (hyponatremia)  1  75/486 (15.43%)  61/492 (12.40%) 
Musculoskeletal and connective tissue disorders     
Muscle weakness, not d/t neuropathy - body/general  1  39/486 (8.02%)  44/492 (8.94%) 
Pain - Back  1  85/486 (17.49%)  86/492 (17.48%) 
Pain - Bone  1  138/486 (28.40%)  156/492 (31.71%) 
Pain - Extremity-limb  1  41/486 (8.44%)  45/492 (9.15%) 
Pain - Joint  1  112/486 (23.05%)  119/492 (24.19%) 
Pain - Muscle  1  119/486 (24.49%)  104/492 (21.14%) 
Nervous system disorders     
Dizziness  1  91/486 (18.72%)  96/492 (19.51%) 
Neuropathy: motor  1  25/486 (5.14%)  43/492 (8.74%) 
Neuropathy: sensory  1  202/486 (41.56%)  223/492 (45.33%) 
Pain - Head/headache  1  70/486 (14.40%)  45/492 (9.15%) 
Taste alteration (dysgeusia)  1  158/486 (32.51%)  132/492 (26.83%) 
Psychiatric disorders     
Insomnia  1  74/486 (15.23%)  80/492 (16.26%) 
Mood alteration - anxiety  1  20/486 (4.12%)  27/492 (5.49%) 
Mood alteration - depression  1  37/486 (7.61%)  28/492 (5.69%) 
Renal and urinary disorders     
Urinary frequency/urgency  1  48/486 (9.88%)  58/492 (11.79%) 
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  1  78/486 (16.05%)  50/492 (10.16%) 
Cough  1  92/486 (18.93%)  80/492 (16.26%) 
Dyspnea (shortness of breath)  1  197/486 (40.53%)  156/492 (31.71%) 
Hemorrhage, pulmonary/upper respiratory - Nose  1  17/486 (3.50%)  29/492 (5.89%) 
Nasal cavity/paranasal sinus reactions  1  40/486 (8.23%)  30/492 (6.10%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  28/486 (5.76%)  33/492 (6.71%) 
Hair loss/Alopecia (scalp or body)  1  201/486 (41.36%)  192/492 (39.02%) 
Nail changes  1  97/486 (19.96%)  149/492 (30.28%) 
Rash/desquamation  1  45/486 (9.26%)  70/492 (14.23%) 
Vascular disorders     
Hot flashes/flushes  1  65/486 (13.37%)  71/492 (14.43%) 
Hypertension  1  14/486 (2.88%)  35/492 (7.11%) 
Hypotension  1  69/486 (14.20%)  42/492 (8.54%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. David I Quinn
Organization: University of Southern California Norris Comprehensive Cancer Center
Phone: 3238653956
Publications of Results:
Goldkorn A, Ely B, Quinn DI, et al.: Results of telomerase activity measurements from live circulating tumor cells captured on a slot microfilter in a phase III SWOG-coordinated prostate cancer trial (S0421). [Abstract] J Clin Oncol 30 (Suppl 15): A-4663, 2012.
Lara P, Ely B, Quinn DI, et al.: SWOG 0421: prognostic and predictive value of bone metabolism biomarkers (BMB) in castration resistant prostate cancer (CRPC) patients (pts) with skeletal metastases treated with docetaxel (DOC) with or without atrasentan (ATR). [Abstract] J Clin Oncol 30 (Suppl 15): A-4547, 2012.
Quinn DI, Tangen CM, Hussain M, et al.: SWOG S0421: phase III study of docetaxel (D) and atrasentan (A) versus docetaxel and placebo (P) for men with advanced castrate resistant prostate cancer (CRPC). [Abstract] J Clin Oncol 30 (Suppl 15): A-4511, 2012.
Goldkorn A, Xu T, Lu B, et al.: Circulating tumor cell capture and analysis in a multicenter SWOG-coordinated prostate cancer trial. [Abstract] J Clin Oncol 28 (Suppl 15): A-TPS342, 2010.
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00134056     History of Changes
Other Study ID Numbers: CDR0000439434
S0421 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted: August 22, 2005
First Posted: August 24, 2005
Results First Submitted: January 4, 2017
Results First Posted: May 2, 2017
Last Update Posted: June 2, 2017