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 : October 27, 2021

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Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

SWOG Cancer Research Network

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

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm I: Placebo	Arm II: Atrasentan
Arm/Group Description	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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
Other	55	56

Baseline Characteristics

Arm/Group Title		Arm I: Placebo	Arm II: Atrasentan	Total
Arm/Group Description		Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...	Total of all reporting groups
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
Baseline Analysis Population Description		...
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. = 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. = Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours. = 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.

Outcome Measures

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.
Description	Measured from date of registration to date of death due to any cause. ...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I: Placebo	Arm II: Atrasentan
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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)

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 (legacy)
	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.
Description	Measured from date of registration to date of first observation of pro...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I: Placebo	Arm II: Atrasentan
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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)

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 (legacy)
	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.
Description	Pain progression is defined as patients reporting an increase of at le...
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

Outcome Measure Data

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
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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
Description	Only adverse events that are possibly, probably or definitely related ...
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

Outcome Measure Data

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
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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.
Description	PSA Partial Response: Greater than or equal to 50% reduction in baseli...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I: Placebo	Arm II: Atrasentan
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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.
Description	Complete Response (CR): Complete disappearance of all measurable and n...
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

Outcome Measure Data

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
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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)
Description	Pain palliation is the proportion of patients showing a two-point redu...
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

Outcome Measure Data

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
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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
Description	Functional status will be measured with the Functional Assessment of C...
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

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I: Placebo	Arm II: Atrasentan Hydrochloride
Arm/Group Description:	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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%

Adverse Events

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
Arm/Group Description	Patients receive docetaxel and pred...	Patients receive docetaxel IV over ...
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	--/--	--/--
Serious Adverse Events 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)
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)

Limitations and Caveats

[Not Specified]

More Information

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

Layout table for Results Point of Contact information

Name/Title:	Dr. David I Quinn
Organization:	University of Southern California Norris Comprehensive Cancer Center
Phone:	3238653956
EMail:	diquinn@med.usc.edu

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, Ely B, Quinn DI, Tangen CM, Fink LM, Xu T, Twardowski P, Van Veldhuizen PJ, Agarwal N, Carducci MA, Monk JP 3rd, Datar RH, Garzotto M, Mack PC, Lara P Jr, Higano CS, Hussain M, Thompson IM Jr, Cote RJ, Vogelzang NJ. Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol. 2014 Apr 10;32(11):1136-42. doi: 10.1200/JCO.2013.51.7417. Epub 2014 Mar 10.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lara PN Jr, Ely B, Quinn DI, Mack PC, Tangen C, Gertz E, Twardowski PW, Goldkorn A, Hussain M, Vogelzang NJ, Thompson IM, Van Loan MD. Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421. J Natl Cancer Inst. 2014 Apr;106(4):dju013. doi: 10.1093/jnci/dju013. Epub 2014 Feb 24.

Quinn DI, Tangen CM, Hussain M, Lara PN Jr, Goldkorn A, Moinpour CM, Garzotto MG, Mack PC, Carducci MA, Monk JP, Twardowski PW, Van Veldhuizen PJ, Agarwal N, Higano CS, Vogelzang NJ, Thompson IM Jr. Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial. Lancet Oncol. 2013 Aug;14(9):893-900. doi: 10.1016/S1470-2045(13)70294-8. Epub 2013 Jul 17.

Layout table for additonal information

Responsible Party:	SWOG Cancer Research Network
ClinicalTrials.gov Identifier:	NCT00134056
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:	October 27, 2021

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