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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

Sponsor
Southwest Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00134056
Collaborator
National Cancer Institute (NCI) (NIH)
1,038
Enrollment
554
Locations
2
Arms
114
Duration (Months)
1.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, prednisone, and atrasentan work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether docetaxel, prednisone, and atrasentan are more effective than docetaxel and prednisone in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying docetaxel, prednisone, and atrasentan to see how well they work compared to docetaxel and prednisone in treating patients with stage IV prostate cancer and bone metastases that did not respond to previous hormone therapy.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

OBJECTIVES:

Primary

  • Compare the survival and progression-free survival of patients with hormone-refractory stage IV prostate cancer and bone metastases treated with docetaxel and prednisone combined with either atrasentan vs placebo.

Secondary

  • Compare pain progression of patients treated with these regimens.

  • Compare the qualitative and quantitative toxicity of these regimens in these patients.

  • Compare the quality of life, in terms of palliation of metastatic bone pain and improvement in functional status, of patients treated with these regimens.

  • Compare prostate-specific antigen (PSA) response rates in patients treated with these regimens.

  • Compare objective response in patients with measurable disease treated with these regimens.

  • Determine whether a 30% reduction in PSA and the slope of PSA from baseline to 3 months is a surrogate marker for survival in patients treated with these regimens.

  • Correlate PSA progression with clinical progression and death in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease progression (measurable or non-measurable disease progression vs prostate-specific antigen progression only), use of bisphosphonates at study entry (yes vs no), worst pain, measured by the Brief Pain Inventory "pain" scale (< grade 4 vs ≥ grade 4), and extraskeletal metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: 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 in the absence of disease progression* or unacceptable toxicity.

  • Arm II: 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 in the absence of disease progression* or unacceptable toxicity.

NOTE: *Patients with PSA progression alone will be allowed to continue treatment

Quality of life is assessed at baseline, before courses 4, 7, and 10, and then after completion of study treatment.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 3 years from study entry.

PROJECTED ACCRUAL: A total of 930 patients will be accrued for this study within 4 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
1038 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer
Study Start Date :
Aug 1, 2006
Actual Primary Completion Date :
Feb 1, 2016
Actual Study Completion Date :
Feb 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm I: placebo

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.

Drug: docetaxel
Docetaxel given IV and prednisone given orally
Other Names:
  • taxotere

    • Drug: prednisone
    Docetaxel given IV and prednisone given orally
    Other Names:
  • steroid

    • Other: placebo
    Given orally
    Experimental: Arm II: atrasentan hydrochloride

    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.

    Drug: atrasentan hydrochloride
    Given orally
    Other Names:
  • atrasentan

    • Drug: docetaxel
    Docetaxel given IV and prednisone given orally
    Other Names:
  • taxotere

    • Drug: prednisone
    Docetaxel given IV and prednisone given orally
    Other Names:
  • steroid

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer. [Up to 7 years after study opens]

      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.

    2. 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. [Up to 7 years after study opens]

      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.

    Secondary Outcome Measures

    1. Compare Pain Progression Between the Two Study Arms. [Up to 52 weeks]

      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.

    2. Compare Qualitative and Quantitative Toxicity Between the Two Study Arms [Assessed every 3 weeks up to 52 weeks]

      Only adverse events that are possibly, probably or definitely related to study drug are reported.

    3. Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm. [Up to 7 years after study opens]

      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.

    4. Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria. [Up to 52 weeks]

      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.

    Other Outcome Measures

    1. Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI) [up to 18 months study period]

      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

    2. Number of Patients With a Change in Functional Status [up to 18 months study period]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    DISEASE CHARACTERISTICS:

    • Histologically confirmed adenocarcinoma of the prostate

    • Stage IV disease (any T, any N, M1b)

    • Evidence of bone metastases by bone scan or MRI

    • Measurable or nonmeasurable disease

    • Soft tissue disease that has been irradiated within the past 2 months is not assessable as measurable disease

    • Hormone-refractory disease despite androgen deprivation and antiandrogen withdrawal, as defined by 1 of the following criteria:

    • Prostate-specific antigen (PSA) progression, defined as 3 consecutive rising PSA levels* taken ≥ 1 week apart

    • PSA ≥ 5 ng/mL NOTE: *If the third confirmatory PSA level is < the second level, the patient is considered eligible provided a fourth PSA level is > the second level

    • Progression of measurable disease

    • Progression of nonmeasurable disease by bone scan

    • Must have undergone surgical or medical (e.g., luteinizing hormone-releasing hormone [LHRH] agonist [e.g., leuprolide or goserelin] or LHRH antagonist therapy) castration

    • Patients who have undergone medical castration must continue LHRH agonist or antagonist therapy during study treatment

    • Must have completed 12 courses of blinding protocol treatment (atrasentan/placebo) AND stopped docetaxel for any reason (including completion of 12 courses) other than progressive disease

    • No symptomatic pleural effusion

    • No third space fluid accumulation (e.g., ascites)

    • No prior or concurrent brain metastases

    • Patients with clinical evidence of brain metastases must have a negative brain CT scan or MRI within the past 8 weeks

    PATIENT CHARACTERISTICS:

    Age

    • 18 and over

    Performance status

    • Zubrod 0-3* NOTE: For a performance status of 3, the cause must be due to pain secondary to bone metastases

    Life expectancy

    • Not specified

    Hematopoietic

    • Not specified

    Hepatic

    • Not specified

    Renal

    • Not specified

    Other

    • Fertile patients must use effective contraception

    • Able to take oral medication without crushing, dissolving, or chewing tablets

    • No major infection

    • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer in complete remission

    • No symptomatic sensory neuropathy ≥ grade 2

    • No history of hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80

    • No other significant, active medical illness that would preclude study treatment or survival

    PRIOR CONCURRENT THERAPY:

    Biologic therapy

    • No more than 1 prior systemic vaccine or biologic therapy

    • At least 4 weeks since prior vaccine or biologic therapy and recovered

    • No concurrent biological response modifiers

    • No concurrent prophylactic colony-stimulating factors

    Chemotherapy

    • More than 2 years since prior adjuvant therapy with a single non-taxane-containing cytotoxic regimen

    • No prior cytotoxic chemotherapy for metastatic prostate cancer

    • No other concurrent chemotherapy

    Endocrine therapy

    • See Disease Characteristics

    • At least 6 weeks since prior bicalutamide or nilutamide AND has subsequent disease progression

    • At least 4 weeks since prior flutamide or ketoconazole AND has subsequent disease progression

    • Prior or concurrent megestrol for treatment of hot flashes allowed

    • No other concurrent corticosteroid or hormonal therapy unless continuing luteinizing hormone-releasing hormone treatment and/or bisphosphonate therapy

    Radiotherapy

    • See Disease Characteristics

    • Prior samarium allowed

    • At least 3 weeks since prior radiotherapy and recovered

    • No prior radiotherapy to ≥ 30% of the bone marrow

    • No prior strontium

    • No concurrent radiotherapy

    Surgery

    • See Disease Characteristics

    • At least 3 weeks since prior surgery and recovered

    Other

    • More than 4 weeks since prior investigational drugs

    • Concurrent bisphosphonates allowed provided therapy is started prior to study entry, dose is maintained during the first 12 weeks of study treatment, and patient meets criteria for disease progression

    • No initiation of bisphosphonates during the first 12 weeks of study treatment

    • No concurrent herbal medications or food supplements (e.g., PC-SPES, saw palmetto, Hypericum perforatum [St. John's wort])

    • Concurrent daily vitamins and calcium supplements allowed

    • At least 14 days since prior and no concurrent administration of any of the following:

    • Antibiotics (e.g., clarithromycin, erythromycin, troleandomycin, rifampin, rifabutin, and rifapentine)

    • Antifungals (e.g., itraconazole, ketoconazole, fluconazole [doses > 200 mg/day], and voriconazole)

    • Antidepressants (e.g., nefazodone and fluvoxamine)

    • Calcium channel blockers (e.g., verapamil, diltiazem)

    • Miscellaneous (e.g., amiodarone [no use within 6 months prior to study entry], grapefruit juice, bitter orange, or modafinil)

    • Anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, and oxcarbazepine)

    • Antibiotics (e.g., rifampin, rifabutin, and rifapentine)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Providence Cancer Center at Providence Hospital Mobile Alabama United States 36608
    2 Alaska Regional Hospital Cancer Center Anchorage Alaska United States 99508
    3 Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital Fairbanks Alaska United States 99701
    4 Mayo Clinic Scottsdale Scottsdale Arizona United States 85259-5499
    5 Arizona Cancer Center at University of Arizona Health Sciences Center Tucson Arizona United States 85724-5024
    6 Hembree Mercy Cancer Center at St. Edward Mercy Medical Center Fort Smith Arkansas United States 72903
    7 East Bay Radiation Oncology Center Castro Valley California United States 94546
    8 Eden Medical Center Castro Valley California United States 94546
    9 Valley Medical Oncology Consultants - Castro Valley Castro Valley California United States 94546
    10 Valley Medical Oncology Fremont California United States 94538
    11 Cancer Care Associates Fresno California United States 93720
    12 Glendale Memorial Hospital Comprehensive Cancer Center Glendale California United States 91204
    13 Rebecca and John Moores UCSD Cancer Center La Jolla California United States 92093-0658
    14 USC/Norris Comprehensive Cancer Center and Hospital Los Angeles California United States 90089-9181
    15 Contra Costa Regional Medical Center Martinez California United States 94553-3156
    16 Tibotec Therapeutics - Division of Ortho Biotech Products, LP Marysville California United States 95901
    17 Community Hospital of the Monterey Peninsula Comprehensive Cancer Center Monterey California United States 93940
    18 Camino Medical Group - Treatment Center Mountain View California United States 94040
    19 El Camino Hospital Cancer Center Mountain View California United States 94040
    20 Highland General Hospital Oakland California United States 94602
    21 Alta Bates Summit Medical Center - Summit Campus Oakland California United States 94609
    22 Bay Area Breast Surgeons, Incorporated Oakland California United States 94609
    23 CCOP - Bay Area Tumor Institute Oakland California United States 94609
    24 Larry G Strieff MD Medical Corporation Oakland California United States 94609
    25 Tom K Lee, Incorporated Oakland California United States 94609
    26 Desert Regional Medical Center Comprehensive Cancer Center Palm Springs California United States 92262
    27 Palo Alto Medical Foundation Palo Alto California United States 94301
    28 PCR Oncology Pismo Beach California United States 93449
    29 Valley Care Medical Center Pleasanton California United States 94588
    30 Valley Medical Oncology Consultants - Pleasanton Pleasanton California United States 94588
    31 Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center Rancho Mirage California United States 92270
    32 University of California Davis Cancer Center Sacramento California United States 95817
    33 Mercy General Hospital Sacramento California United States 95819
    34 Salinas Valley Memorial Hospital Salinas California United States 93901
    35 Doctors Medical Center - San Pablo Campus San Pablo California United States 94806
    36 Tahoe Forest Cancer Center Truckee California United States 96161
    37 Aurora Presbyterian Hospital Aurora Colorado United States 80012
    38 University of Colorado Cancer Center at UC Health Sciences Center Aurora Colorado United States 80045
    39 Boulder Community Hospital Boulder Colorado United States 80301-9019
    40 Penrose Cancer Center at Penrose Hospital Colorado Springs Colorado United States 80933
    41 Denver Health Medical Center Denver Colorado United States 80204
    42 St. Anthony Central Hospital Denver Colorado United States 80204
    43 Porter Adventist Hospital Denver Colorado United States 80210
    44 Presbyterian - St. Luke's Medical Center Denver Colorado United States 80218
    45 St. Joseph Hospital Denver Colorado United States 80218
    46 Rose Medical Center Denver Colorado United States 80220
    47 Veterans Affairs Medical Center - Denver Denver Colorado United States 80220
    48 CCOP - Colorado Cancer Research Program Denver Colorado United States 80224-2522
    49 Shaw Regional Cancer Center Edwards Colorado United States 81632
    50 Swedish Medical Center Englewood Colorado United States 80110
    51 Poudre Valley Hospital Fort Collins Colorado United States 80524
    52 Front Range Cancer Specialists Fort Collins Colorado United States 80528
    53 Valley View Hospital Cancer Center Glenwood Springs Colorado United States 81601
    54 St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center Grand Junction Colorado United States 81502
    55 North Colorado Medical Center Greeley Colorado United States 80631
    56 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    57 Hope Cancer Care Center at Longmont United Hospital Longmont Colorado United States 80501
    58 McKee Medical Center Loveland Colorado United States 80539
    59 Montrose Memorial Hospital Cancer Center Montrose Colorado United States 81401
    60 St. Mary - Corwin Regional Medical Center Pueblo Colorado United States 81004
    61 North Suburban Medical Center Thornton Colorado United States 80229
    62 Exempla Lutheran Medical Center Wheat Ridge Colorado United States 80033
    63 Praxair Cancer Center at Danbury Hospital Danbury Connecticut United States 06810
    64 Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford Connecticut United States 06105
    65 Manchester Memorial Hospital Manchester Connecticut United States 06040
    66 Middlesex Hospital Cancer Center Middletown Connecticut United States 06457
    67 Connecticut Oncology & Hematology - Torrington Torrington Connecticut United States 06790
    68 CCOP - Christiana Care Health Services Newark Delaware United States 19713
    69 Lombardi Comprehensive Cancer Center at Georgetown University Medical Center Washington District of Columbia United States 20007
    70 Sibley Memorial Hospital Washington District of Columbia United States 20016
    71 Veterans Affairs Medical Center - Washington, DC Washington District of Columbia United States 20422
    72 Broward General Medical Center Cancer Center Fort Lauderdale Florida United States 33316
    73 Memorial Cancer Institute at Memorial Regional Hospital Hollywood Florida United States 33021
    74 Cancer Centers of Central Florida, PA Leesburg Florida United States 34788
    75 University of Miami Sylvester Comprehensive Cancer Center - Miami Miami Florida United States 33136
    76 Integrated Community Oncology Network - Orange Park Orange Park Florida United States 32073
    77 Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando Florida United States 32803-1273
    78 Sacred Heart Cancer Center at Sacred Heart Hospital Pensacola Florida United States 32504
    79 West Florida Cancer Institute at West Florida Hospital - Pensacola Pensacola Florida United States 32514
    80 Space Coast Medical Associates Titusville Florida United States 32796
    81 Northeast Georgia Cancer Care, LLC - Medical Oncology Athens Georgia United States 30607
    82 Piedmont Hospital Atlanta Georgia United States 30309
    83 Northside Hospital Cancer Center Atlanta Georgia United States 30342-1611
    84 Saint Joseph's Hospital of Atlanta Atlanta Georgia United States 30342-1701
    85 CCOP - Atlanta Regional Atlanta Georgia United States 30342
    86 MBCCOP - Medical College of Georgia Cancer Center Augusta Georgia United States 30912
    87 WellStar Cobb Hospital Austell Georgia United States 30106
    88 Charles B. Eberhart Cancer Center at DeKalb Medical Center Decatur Georgia United States 30033
    89 Gwinnett Medical Center Lawrenceville Georgia United States 30045
    90 Kennestone Cancer Center at Wellstar Kennestone Hospital Marietta Georgia United States 30060
    91 Southern Regional Medical Center Riverdale Georgia United States 30274-2600
    92 Harbin Clinic Cancer Center - Medical Oncology Rome Georgia United States 30165
    93 Kapiolani Medical Center at Pali Momi 'Aiea Hawaii United States 96701
    94 Cancer Research Center of Hawaii Honolulu Hawaii United States 96813
    95 OnCare Hawaii, Incorporated - Lusitana Honolulu Hawaii United States 96813
    96 Queen's Cancer Institute at Queen's Medical Center Honolulu Hawaii United States 96813
    97 Straub Clinic and Hospital, Incorporated Honolulu Hawaii United States 96813
    98 Hawaii Medical Center - East Honolulu Hawaii United States 96817
    99 OnCare Hawaii, Incorporated - Kuakini Honolulu Hawaii United States 96817
    100 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
    101 Tripler Army Medical Center Honolulu Hawaii United States 96859
    102 Maui Memorial Medical Center Wailuku Hawaii United States 96793
    103 Pacific Cancer Institute - Maui Wailuku Hawaii United States 96793
    104 Mountain States Tumor Institute at St. Luke's Regional Medical Center Boise Idaho United States 83712
    105 Saint Anthony's Hospital at Saint Anthony's Health Center Alton Illinois United States 62002
    106 Rush-Copley Cancer Care Center Aurora Illinois United States 60504
    107 Mount Sinai Hospital Medical Center Chicago Illinois United States 60608
    108 University of Illinois Cancer Center Chicago Illinois United States 60612-7243
    109 Resurrection Medical Center Chicago Illinois United States 60631
    110 Creticos Cancer Center at Advocate Illinois Masonic Medical Center Chicago Illinois United States 60657
    111 Decatur Memorial Hospital Cancer Care Institute Decatur Illinois United States 62526
    112 Sherman Hospital Elgin Illinois United States 60123
    113 Alexian Brothers Radiation Oncology Elk Grove Village Illinois United States 60007
    114 Elmhurst Memorial Hospital Elmhurst Illinois United States 60126
    115 Evanston Hospital Evanston Illinois United States 60201-1781
    116 Leonard C. Ferguson Cancer Center Freeport Illinois United States 61032
    117 Ingalls Cancer Care Center at Ingalls Memorial Hospital Harvey Illinois United States 60426
    118 Veterans Affairs Medical Center - Hines Hines Illinois United States 60141
    119 Joliet Oncology-Hematology Associates, Limited - West Joliet Illinois United States 60435
    120 Provena St. Mary's Regional Cancer Center - Kankakee Kankakee Illinois United States 60901
    121 La Grange Memorial Hospital La Grange Illinois United States 60525
    122 Cardinal Bernardin Cancer Center at Loyola University Medical Center Maywood Illinois United States 60153
    123 Good Samaritan Regional Health Center Mount Vernon Illinois United States 62864
    124 Edward Hospital Cancer Center Naperville Illinois United States 60540
    125 Hematology Oncology Consultants - Naperville Naperville Illinois United States 60540
    126 Swedish-American Regional Cancer Center Rockford Illinois United States 61104-2315
    127 Regional Cancer Center at Memorial Medical Center Springfield Illinois United States 62781-0001
    128 Carle Cancer Center at Carle Foundation Hospital Urbana Illinois United States 61801
    129 CCOP - Carle Cancer Center Urbana Illinois United States 61801
    130 Central Dupage Cancer Center Winfield Illinois United States 60190
    131 St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove Indiana United States 46107
    132 Bloomington Hospital Regional Cancer Institute Bloomington Indiana United States 47403
    133 Elkhart General Hospital Elkhart Indiana United States 46515
    134 Center for Cancer Care at Goshen General Hospital Goshen Indiana United States 46526
    135 Indiana University Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202-5289
    136 Veterans Affairs Medical Center - Indianapolis Indianapolis Indiana United States 46202
    137 William N. Wishard Memorial Hospital Indianapolis Indiana United States 46202
    138 Howard Community Hospital Kokomo Indiana United States 46904
    139 Center for Cancer Therapy at LaPorte Hospital and Health Services La Porte Indiana United States 46350
    140 Clarian Arnett Cancer Care Lafayette Indiana United States 47904
    141 Saint Anthony Memorial Health Centers Michigan City Indiana United States 46360
    142 Medical Consultants, PC at Ball Memorial Cancer Center Muncie Indiana United States 47303
    143 Community Hospital Munster Indiana United States 46321
    144 Reid Hospital & Health Care Services Richmond Indiana United States 47374
    145 CCOP - Northern Indiana CR Consortium South Bend Indiana United States 46601
    146 Memorial Hospital of South Bend South Bend Indiana United States 46601
    147 Saint Joseph Regional Medical Center South Bend Indiana United States 46617
    148 South Bend Clinic South Bend Indiana United States 46617
    149 McFarland Clinic, PC Ames Iowa United States 50010
    150 Hematology Oncology Associates of the Quad Cities Bettendorf Iowa United States 52722
    151 Iowa Blood and Cancer Care Cedar Rapids Iowa United States 52402
    152 St. Luke's Hospital Cedar Rapids Iowa United States 52402
    153 Mercy Regional Cancer Center at Mercy Medical Center Cedar Rapids Iowa United States 52403
    154 Medical Oncology and Hematology Associates - West Des Moines Clive Iowa United States 50325
    155 Heartland Oncology and Hematology Council Bluffs Iowa United States 51503
    156 Genesis Regional Cancer Center at Genesis Medical Center Davenport Iowa United States 52803
    157 Genesis Medical Center - West Campus Davenport Iowa United States 52804
    158 Mercy Capitol Hospital Des Moines Iowa United States 50307
    159 CCOP - Iowa Oncology Research Association Des Moines Iowa United States 50309
    160 John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines Iowa United States 50309
    161 Medical Oncology and Hematology Associates at John Stoddard Cancer Center Des Moines Iowa United States 50309
    162 Medical Oncology and Hematology Associates at Mercy Cancer Center Des Moines Iowa United States 50314
    163 Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    164 John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines Iowa United States 50316
    165 McCreery Cancer Center at Ottumwa Regional Ottumwa Iowa United States 52501
    166 Siouxland Hematology-Oncology Associates, LLP Sioux City Iowa United States 51101
    167 Mercy Medical Center - Sioux City Sioux City Iowa United States 51104
    168 St. Luke's Regional Medical Center Sioux City Iowa United States 51104
    169 Cedar Valley Medical Specialists, PC - West Ridgeway Avenue Waterloo Iowa United States 50701
    170 Covenant Cancer Treatment Center Waterloo Iowa United States 50702
    171 Hospital District Sixth of Harper County Anthony Kansas United States 67003
    172 Cancer Center of Kansas, PA - Chanute Chanute Kansas United States 66720
    173 Cancer Center of Kansas, PA - Dodge City Dodge City Kansas United States 67801
    174 Cancer Center of Kansas, PA - El Dorado El Dorado Kansas United States 67042
    175 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
    176 Cancer Center of Kansas-Independence Independence Kansas United States 67301
    177 Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City Kansas United States 66160-7357
    178 Cancer Center of Kansas, PA - Kingman Kingman Kansas United States 67068
    179 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    180 Southwest Medical Center Liberal Kansas United States 67901
    181 Cancer Center of Kansas, PA - Newton Newton Kansas United States 67114
    182 Menorah Medical Center Overland Park Kansas United States 66209
    183 Saint Luke's Hospital - South Overland Park Kansas United States 66213
    184 Cancer Center of Kansas, PA - Parsons Parsons Kansas United States 67357
    185 Cancer Center of Kansas, PA - Pratt Pratt Kansas United States 67124
    186 Cancer Center of Kansas, PA - Salina Salina Kansas United States 67401
    187 Tammy Walker Cancer Center at Salina Regional Health Center Salina Kansas United States 67401
    188 Shawnee Mission Medical Center Shawnee Mission Kansas United States 66204
    189 Cotton-O'Neil Cancer Center Topeka Kansas United States 66606
    190 St. Francis Comprehensive Cancer Center Topeka Kansas United States 66606
    191 Cancer Center of Kansas, PA - Wellington Wellington Kansas United States 67152
    192 Associates in Womens Health, PA - North Review Wichita Kansas United States 67208
    193 Cancer Center of Kansas, PA - Medical Arts Tower Wichita Kansas United States 67208
    194 Cancer Center of Kansas, PA - Wichita Wichita Kansas United States 67214
    195 CCOP - Wichita Wichita Kansas United States 67214
    196 Via Christi Cancer Center at Via Christi Regional Medical Center Wichita Kansas United States 67214
    197 Cancer Center of Kansas, PA - Winfield Winfield Kansas United States 67156
    198 James Graham Brown Cancer Center at University of Louisville Louisville Kentucky United States 40292
    199 Pennington Cancer Center at Baton Rouge General Baton Rouge Louisiana United States 70806
    200 Mary Bird Perkins Cancer Center - Baton Rouge Baton Rouge Louisiana United States 70809
    201 MBCCOP - LSU Health Sciences Center New Orleans Louisiana United States 70112
    202 Medical Center of Louisiana - New Orleans New Orleans Louisiana United States 70112
    203 Highland Clinic Shreveport Louisiana United States 71105
    204 Feist-Weiller Cancer Center at Louisiana State University Health Sciences Shreveport Louisiana United States 71130-3932
    205 Greater Baltimore Medical Center Cancer Center Baltimore Maryland United States 21204
    206 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231-2410
    207 Shore Regional Cancer Center at Memorial Hospital - Easton Easton Maryland United States 21601
    208 Union Hospital Cancer Program at Union Hospital Elkton Maryland United States 21921
    209 Boston University Cancer Research Center Boston Massachusetts United States 02118
    210 Lahey Clinic Medical Center - Burlington Burlington Massachusetts United States 01805
    211 MetroWest Medical Center - Framingham Union Hospital Framingham Massachusetts United States 01702
    212 Baystate Regional Cancer Program at D'Amour Center for Cancer Care Springfield Massachusetts United States 01199
    213 Hickman Cancer Center at Bixby Medical Center Adrian Michigan United States 49221
    214 Saint Joseph Mercy Cancer Center Ann Arbor Michigan United States 48106-0995
    215 CCOP - Michigan Cancer Research Consortium Ann Arbor Michigan United States 48106
    216 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109-0942
    217 Battle Creek Health System Cancer Care Center Battle Creek Michigan United States 49017
    218 Mecosta County Medical Center Big Rapids Michigan United States 49307
    219 Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn Michigan United States 48123-2500
    220 Josephine Ford Cancer Center at Henry Ford Hospital Detroit Michigan United States 48202
    221 Green Bay Oncology, Limited - Escanaba Escanaba Michigan United States 49431
    222 Genesys Hurley Cancer Institute Flint Michigan United States 48503
    223 Hurley Medical Center Flint Michigan United States 48503
    224 Butterworth Hospital at Spectrum Health Grand Rapids Michigan United States 49503
    225 CCOP - Grand Rapids Grand Rapids Michigan United States 49503
    226 Lacks Cancer Center at Saint Mary's Health Care Grand Rapids Michigan United States 49503
    227 Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods Michigan United States 48236
    228 Dickinson County Healthcare System Iron Mountain Michigan United States 49801
    229 Foote Memorial Hospital Jackson Michigan United States 49201
    230 Borgess Medical Center Kalamazoo Michigan United States 49001
    231 West Michigan Cancer Center Kalamazoo Michigan United States 49007-3731
    232 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    233 Haematology-Oncology Associates of Ohio and Michigan, PC Lambertville Michigan United States 48144
    234 Sparrow Regional Cancer Center Lansing Michigan United States 48912-1811
    235 St. Mary Mercy Hospital Livonia Michigan United States 48154
    236 Upper Michigan Cancer Center at Marquette General Hospital Marquette Michigan United States 49855
    237 Community Cancer Center of Monroe Monroe Michigan United States 48162
    238 Mercy Memorial Hospital - Monroe Monroe Michigan United States 48162
    239 Clemens Regional Medical Center Mount Clemens Michigan United States 48043
    240 Mercy General Health Partners Muskegon Michigan United States 49443
    241 St. Joseph Mercy Oakland Pontiac Michigan United States 48341-2985
    242 Mercy Regional Cancer Center at Mercy Hospital Port Huron Michigan United States 48060
    243 Seton Cancer Institute at Saint Mary's - Saginaw Saginaw Michigan United States 48601
    244 Lakeland Regional Cancer Care Center - St. Joseph Saint Joseph Michigan United States 49085
    245 Providence Cancer Institute at Providence Hospital - Southfield Campus Southfield Michigan United States 48075
    246 Munson Medical Center Traverse City Michigan United States 49684
    247 St. John Macomb Hospital Warren Michigan United States 48093
    248 Metro Health Hospital Wyoming Michigan United States 49519
    249 MeritCare Bemidji Bemidji Minnesota United States 56601
    250 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    251 Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids Minnesota United States 55433
    252 Duluth Clinic Cancer Center - Duluth Duluth Minnesota United States 55805-1983
    253 CCOP - Duluth Duluth Minnesota United States 55805
    254 Miller - Dwan Medical Center Duluth Minnesota United States 55805
    255 Fairview Southdale Hospital Edina Minnesota United States 55435
    256 Fergus Falls Medical Group, PA Fergus Falls Minnesota United States 56537
    257 Mercy and Unity Cancer Center at Unity Hospital Fridley Minnesota United States 55432
    258 Minnesota Oncology Hematology, PA - Maplewood Maplewood Minnesota United States 55109
    259 Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis Minnesota United States 55407
    260 Veterans Affairs Medical Center - Minneapolis Minneapolis Minnesota United States 55417
    261 Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale Minnesota United States 55422-2900
    262 Mayo Clinic Cancer Center Rochester Minnesota United States 55905
    263 CentraCare Clinic - River Campus Saint Cloud Minnesota United States 56303
    264 Coborn Cancer Center Saint Cloud Minnesota United States 56303
    265 CCOP - Metro-Minnesota Saint Louis Park Minnesota United States 55416
    266 Park Nicollet Cancer Center Saint Louis Park Minnesota United States 55416
    267 United Hospital Saint Paul Minnesota United States 55102
    268 St. Francis Cancer Center at St. Francis Medical Center Shakopee Minnesota United States 55379
    269 Ridgeview Medical Center Waconia Minnesota United States 55387
    270 Willmar Cancer Center at Rice Memorial Hospital Willmar Minnesota United States 56201
    271 Minnesota Oncology Hematology, PA - Woodbury Woodbury Minnesota United States 55125
    272 University of Mississippi Cancer Clinic Jackson Mississippi United States 39216
    273 Veterans Affairs Medical Center - Jackson Jackson Mississippi United States 39216
    274 Regional Cancer Center at Singing River Hospital Pascagoula Mississippi United States 39581
    275 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    276 Saint Luke's Hospital Chesterfield Missouri United States 63017
    277 Independence Regional Health Center Independence Missouri United States 64050
    278 Freeman Cancer Institute at Freeman Health System Joplin Missouri United States 64804
    279 Truman Medical Center - Hospital Hill Kansas City Missouri United States 64108
    280 Saint Luke's Cancer Institute at Saint Luke's Hospital Kansas City Missouri United States 64111
    281 St. Joseph Medical Center Kansas City Missouri United States 64114
    282 North Kansas City Hospital Kansas City Missouri United States 64116
    283 Parvin Radiation Oncology Kansas City Missouri United States 64116
    284 Heartland Hematology Oncology Associates, Incorporated Kansas City Missouri United States 64118
    285 Veterans Affairs Medical Center - Kansas City Kansas City Missouri United States 64128
    286 CCOP - Kansas City Kansas City Missouri United States 64131
    287 Research Medical Center Kansas City Missouri United States 64132
    288 Saint Luke's East - Lee's Summit Lee's Summit Missouri United States 64086
    289 Liberty Hospital Liberty Missouri United States 64068
    290 Heartland Regional Medical Center Saint Joseph Missouri United States 64506
    291 Midwest Hematology Oncology Group, Incorporated Saint Louis Missouri United States 63109
    292 Missouri Baptist Cancer Center Saint Louis Missouri United States 63131
    293 Arch Medical Services, Incorporated at Center for Cancer Care and Research Saint Louis Missouri United States 63141
    294 CCOP - St. Louis-Cape Girardeau Saint Louis Missouri United States 63141
    295 David C. Pratt Cancer Center at St. John's Mercy Saint Louis Missouri United States 63141
    296 CCOP - Montana Cancer Consortium Billings Montana United States 59101
    297 Hematology-Oncology Centers of the Northern Rockies - Billings Billings Montana United States 59101
    298 Northern Rockies Radiation Oncology Center Billings Montana United States 59101
    299 St. Vincent Healthcare Cancer Care Services Billings Montana United States 59101
    300 Billings Clinic - Downtown Billings Montana United States 59107-7000
    301 Bozeman Deaconess Cancer Center Bozeman Montana United States 59715
    302 St. James Healthcare Cancer Care Butte Montana United States 59701
    303 Big Sky Oncology Great Falls Montana United States 59405-5309
    304 Frontier Cancer Center Great Falls Montana United States 59405
    305 Great Falls Clinic - Main Facility Great Falls Montana United States 59405
    306 Sletten Cancer Institute at Benefis Healthcare Great Falls Montana United States 59405
    307 Northern Montana Hospital Havre Montana United States 59501
    308 St. Peter's Hospital Helena Montana United States 59601
    309 Glacier Oncology, PLLC Kalispell Montana United States 59901
    310 Kalispell Medical Oncology at KRMC Kalispell Montana United States 59901
    311 Kalispell Regional Medical Center Kalispell Montana United States 59901
    312 Community Medical Center Missoula Montana United States 59801
    313 Guardian Oncology and Center for Wellness Missoula Montana United States 59804
    314 Montana Cancer Specialists at Montana Cancer Center Missoula Montana United States 59807-7877
    315 Montana Cancer Center at St. Patrick Hospital and Health Sciences Center Missoula Montana United States 59807
    316 Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center Grand Island Nebraska United States 68803
    317 Good Samaritan Cancer Center at Good Samaritan Hospital Kearney Nebraska United States 68848-1990
    318 Callahan Cancer Center at Great Plains Regional Medical Center North Platte Nebraska United States 69103
    319 UNMC Eppley Cancer Center at the University of Nebraska Medical Center Omaha Nebraska United States 68198-6805
    320 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    321 CCOP - Nevada Cancer Research Foundation Las Vegas Nevada United States 89106
    322 Nevada Cancer Institute Las Vegas Nevada United States 89135
    323 Renown Institute for Cancer at Renown Regional Medical Center Reno Nevada United States 89502
    324 New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care Concord New Hampshire United States 03301
    325 Center for Cancer Care at Exeter Hospital Exeter New Hampshire United States 03833
    326 New Hampshire Oncology - Hematology, PA - Hooksett Hooksett New Hampshire United States 03106
    327 Lakes Region General Hospital Laconia New Hampshire United States 03246
    328 Veterans Affairs Medical Center - East Orange East Orange New Jersey United States 07018-1095
    329 Hunterdon Regional Cancer Center at Hunterdon Medical Center Flemington New Jersey United States 08822
    330 Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton Marlton New Jersey United States 08053
    331 Jersey Shore Cancer Center at Jersey Shore University Medical Center Neptune New Jersey United States 07754-0397
    332 Valley Hospital - Ridgewood Ridgewood New Jersey United States 07450
    333 Somerset Medical Center Somerville New Jersey United States 08876
    334 Frederick R. and Betty M. Smith Cancer Treatment Center Sparta New Jersey United States 07871
    335 Cancer Institute of New Jersey at Cooper - Voorhees Voorhees New Jersey United States 08043
    336 Fox Chase Virtua Health Cancer Program at Virtua West Jersey Voorhees New Jersey United States 08043
    337 Our Lady of Mercy Medical Center Comprehensive Cancer Center Bronx New York United States 10466
    338 Veterans Affairs Medical Center - Brooklyn Brooklyn New York United States 11209
    339 Veterans Affairs Medical Center - Buffalo Buffalo New York United States 14215
    340 Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital Cooperstown New York United States 13326
    341 CCOP - Hematology-Oncology Associates of Central New York East Syracuse New York United States 13057
    342 Falck Cancer Center at Arnot Ogden Medical Center Elmira New York United States 14905
    343 Northern Westchester Hospital Mount Kisco New York United States 10549
    344 New York Weill Cornell Cancer Center at Cornell University New York New York United States 10021
    345 Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center New York New York United States 10032
    346 Interlakes Oncology/Hematology PC Rochester New York United States 14623
    347 James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester New York United States 14642
    348 Nalitt Cancer Institute at Staten Island University Hospital Staten Island New York United States 10305
    349 Stony Brook University Cancer Center Stony Brook New York United States 11794-9446
    350 SUNY Upstate Medical University Hospital Syracuse New York United States 13210
    351 Veterans Affairs Medical Center - Syracuse Syracuse New York United States 13210
    352 Randolph Hospital Asheboro North Carolina United States 27203-5400
    353 Mission Hospitals - Memorial Campus Asheville North Carolina United States 28801
    354 Alamance Cancer Center at Alamance Regional Medical Center Burlington North Carolina United States 27216
    355 Presbyterian Cancer Center at Presbyterian Hospital Charlotte North Carolina United States 28233-3549
    356 Veterans Affairs Medical Center - Durham Durham North Carolina United States 27705
    357 Southeastern Medical Oncology Center - Goldsboro Goldsboro North Carolina United States 27534
    358 Wayne Memorial Hospital, Incorporated Goldsboro North Carolina United States 27534
    359 Moses Cone Regional Cancer Center at Wesley Long Community Hospital Greensboro North Carolina United States 27403-1198
    360 Kinston Medical Specialists Kinston North Carolina United States 28501
    361 Annie Penn Cancer Center Reidsville North Carolina United States 27320
    362 Rutherford Hospital Rutherfordton North Carolina United States 28139
    363 Marion L. Shepard Cancer Center at Beaufort County Hospital Washington North Carolina United States 27889
    364 Bismarck Cancer Center Bismarck North Dakota United States 58501
    365 Medcenter One Hospital Cancer Care Center Bismarck North Dakota United States 58501
    366 Mid Dakota Clinic, PC Bismarck North Dakota United States 58501
    367 St. Alexius Medical Center Cancer Center Bismarck North Dakota United States 58502
    368 Dakota Cancer Institute at Dakota Clinic - South University Fargo North Dakota United States 58103
    369 CCOP - MeritCare Hospital Fargo North Dakota United States 58122
    370 MeritCare Broadway Fargo North Dakota United States 58122
    371 Trinity CancerCare Center Minot North Dakota United States 58701
    372 McDowell Cancer Center at Akron General Medical Center Akron Ohio United States 44307
    373 Wood County Oncology Center Bowling Green Ohio United States 43402
    374 Veterans Affairs Medical Center - Cincinnati Cincinnati Ohio United States 45220
    375 Charles M. Barrett Cancer Center at University Hospital Cincinnati Ohio United States 45267
    376 MetroHealth Cancer Care Center at MetroHealth Medical Center Cleveland Ohio United States 44109
    377 North Coast Cancer Care - Clyde Clyde Ohio United States 43410
    378 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210-1240
    379 Grandview Hospital Dayton Ohio United States 45405
    380 Good Samaritan Hospital Dayton Ohio United States 45406
    381 David L. Rike Cancer Center at Miami Valley Hospital Dayton Ohio United States 45409
    382 Samaritan North Cancer Care Center Dayton Ohio United States 45415
    383 CCOP - Dayton Dayton Ohio United States 45420
    384 Veterans Affairs Medical Center - Dayton Dayton Ohio United States 45428
    385 Hematology Oncology Center Elyria Ohio United States 44035
    386 Blanchard Valley Medical Associates Findlay Ohio United States 45840
    387 Middletown Regional Hospital Franklin Ohio United States 45005-1066
    388 Wayne Hospital Greenville Ohio United States 45331
    389 Charles F. Kettering Memorial Hospital Kettering Ohio United States 45429
    390 St. Rita's Medical Center Lima Ohio United States 45801
    391 Northwest Ohio Oncology Center Maumee Ohio United States 43537-1839
    392 St. Luke's Hospital Maumee Ohio United States 43537
    393 Fisher-Titus Medical Center Norwalk Ohio United States 44857
    394 St. Charles Mercy Hospital Oregon Ohio United States 43616
    395 Toledo Clinic - Oregon Oregon Ohio United States 43616
    396 North Coast Cancer Care, Incorporated Sandusky Ohio United States 44870
    397 Flower Hospital Cancer Center Sylvania Ohio United States 43560
    398 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
    399 Toledo Hospital Toledo Ohio United States 43606
    400 St. Vincent Mercy Medical Center Toledo Ohio United States 43608
    401 Medical University of Ohio Cancer Center Toledo Ohio United States 43614
    402 CCOP - Toledo Community Hospital Toledo Ohio United States 43617
    403 St. Anne Mercy Hospital Toledo Ohio United States 43623
    404 Toledo Clinic, Incorporated - Main Clinic Toledo Ohio United States 43623
    405 UVMC Cancer Care Center at Upper Valley Medical Center Troy Ohio United States 45373-1300
    406 Fulton County Health Center Wauseon Ohio United States 43567
    407 Clinton Memorial Hospital Wilmington Ohio United States 45177
    408 United States Air Force Medical Center - Wright-Patterson Wright-Patterson Air Force Base Ohio United States 45433-5529
    409 Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia Ohio United States 45385
    410 Cleo Craig Cancer Research Clinic Lawton Oklahoma United States 73505
    411 Bay Area Hospital Coos Bay Oregon United States 97420
    412 Providence Milwaukie Hospital Milwaukie Oregon United States 97222
    413 Providence Cancer Center at Providence Portland Medical Center Portland Oregon United States 97213-2967
    414 Adventist Medical Center Portland Oregon United States 97216
    415 CCOP - Columbia River Oncology Program Portland Oregon United States 97225
    416 Providence St. Vincent Medical Center Portland Oregon United States 97225
    417 Kaiser Permanente Health Care - Portland Portland Oregon United States 97232
    418 Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest Allentown Pennsylvania United States 18105
    419 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    420 Geisinger Cancer Institute at Geisinger Health Danville Pennsylvania United States 17822-0001
    421 Easton Regional Cancer Center at Easton Hospital Easton Pennsylvania United States 18042
    422 Geisinger Hazleton Cancer Center Hazleton Pennsylvania United States 18201
    423 Cancer Center of Paoli Memorial Hospital Paoli Pennsylvania United States 19301-1792
    424 Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia Pennsylvania United States 19107-5541
    425 Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital Pittsburgh Pennsylvania United States 15224-1791
    426 Guthrie Cancer Center at Guthrie Clinic Sayre Sayre Pennsylvania United States 18840
    427 Hematology and Oncology Associates of Northeastern Pennsylvania Scranton Pennsylvania United States 18508
    428 Geisinger Medical Group - Scenery Park State College Pennsylvania United States 16801
    429 Mount Nittany Medical Center State College Pennsylvania United States 16803
    430 Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre Pennsylvania United States 18711
    431 CCOP - Main Line Health Wynnewood Pennsylvania United States 19096
    432 Lankenau Cancer Center at Lankenau Hospital Wynnewood Pennsylvania United States 19096
    433 AnMed Cancer Center Anderson South Carolina United States 29621
    434 Hollings Cancer Center at Medical University of South Carolina Charleston South Carolina United States 29425
    435 McLeod Regional Medical Center Florence South Carolina United States 29501
    436 CCOP - Upstate Carolina Spartanburg South Carolina United States 29303
    437 Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg South Carolina United States 29303
    438 Oncology Services of Aberdeen Aberdeen South Dakota United States 57401
    439 Rapid City Regional Hospital Rapid City South Dakota United States 57701
    440 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    441 Medical X-Ray Center, PC Sioux Falls South Dakota United States 57105
    442 Sanford Cancer Center at Sanford USD Medical Center Sioux Falls South Dakota United States 57117-5039
    443 Cookeville Regional Medical Center Cookeville Tennessee United States 38501
    444 Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center Kingsport Tennessee United States 37662
    445 Thompson Cancer Survival Center Knoxville Tennessee United States 37916
    446 University of Tennessee Cancer Institute - Memphis Memphis Tennessee United States 38104
    447 Veterans Affairs Medical Center - Memphis Memphis Tennessee United States 38104
    448 Harrington Cancer Center Amarillo Texas United States 79106
    449 St. Joseph Regional Cancer Center Bryan Texas United States 77802
    450 Veterans Affairs Medical Center - Dallas Dallas Texas United States 75216
    451 Medical City Dallas Hospital Dallas Texas United States 75230
    452 Brooke Army Medical Center Fort Sam Houston Texas United States 78234-6200
    453 Baylor University Medical Center - Houston Houston Texas United States 77030
    454 Ben Taub General Hospital Houston Texas United States 77030
    455 Methodist Hospital Houston Texas United States 77030
    456 St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital Houston Texas United States 77030
    457 Veterans Affairs Medical Center - Houston Houston Texas United States 77030
    458 Wilford Hall Medical Center Lackland Air Force Base Texas United States 78236
    459 UMC Southwest Cancer and Research Center Lubbock Texas United States 79415-3364
    460 Veterans Affairs Medical Center - San Antonio (Murphy) San Antonio Texas United States 78209
    461 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229-3900
    462 Cancer Therapy and Research Center San Antonio Texas United States 78229
    463 University Hospital - San Antonio San Antonio Texas United States 78229
    464 CCOP - Scott and White Hospital Temple Texas United States 76508
    465 American Fork Hospital American Fork Utah United States 84003
    466 Sandra L. Maxwell Cancer Center Cedar City Utah United States 84720
    467 Logan Regional Hospital Logan Utah United States 84321
    468 Jon and Karen Huntsman Cancer Center at Intermountain Medical Center Murray Utah United States 84157
    469 Val and Ann Browning Cancer Center at McKay-Dee Hospital Center Ogden Utah United States 84403
    470 Utah Valley Regional Medical Center - Provo Provo Utah United States 84604
    471 Dixie Regional Medical Center - East Campus Saint George Utah United States 84770
    472 LDS Hospital Salt Lake City Utah United States 84103
    473 Utah Cancer Specialists at UCS Cancer Center Salt Lake City Utah United States 84106
    474 Huntsman Cancer Institute at University of Utah Salt Lake City Utah United States 84112
    475 Green Mountain Oncology Group Bennington Vermont United States 05201
    476 Danville Regional Medical Center Danville Virginia United States 24541
    477 Fredericksburg Oncology, Incorporated Fredericksburg Virginia United States 22401
    478 Riverside Middle Peninsula Cancer Center Gloucester Virginia United States 23061
    479 Lynchburg Hematology-Oncology Clinic Lynchburg Virginia United States 24501
    480 Peninsula Cancer Institute - Newport News Office Newport News Virginia United States 23601
    481 Southwest Virginia Regional Cancer Center at Wellmonth Health Norton Virginia United States 24273
    482 Veterans Affairs Medical Center - Richmond Richmond Virginia United States 23249
    483 Virginia Commonwealth University Massey Cancer Center Richmond Virginia United States 23298-0037
    484 Peninsula Cancer Institute - Williamsburg Office Williamsburg Virginia United States 23185
    485 Auburn Regional Center for Cancer Care Auburn Washington United States 98002
    486 St. Joseph Cancer Center Bellingham Washington United States 98225
    487 Olympic Hematology and Oncology Bremerton Washington United States 98310
    488 Providence Centralia Hospital Centralia Washington United States 98531-9027
    489 St. Francis Hospital Federal Way Washington United States 98003
    490 Columbia Basin Hematology Kennewick Washington United States 99336
    491 Cascade Cancer Center at Evergreen Hospital Medical Center Kirkland Washington United States 98033
    492 Providence St. Peter Hospital Regional Cancer Center Olympia Washington United States 98506-5166
    493 Harrison Poulsbo Hematology and Onocology Poulsbo Washington United States 98370
    494 Good Samaritan Cancer Center Puyallup Washington United States 98372
    495 Valley Medical Center Renton Washington United States 98055
    496 CCOP - Virginia Mason Research Center Seattle Washington United States 98101
    497 Harborview Medical Center Seattle Washington United States 98104
    498 Minor and James Medical, PLLC Seattle Washington United States 98104
    499 Pacific Medical Center Seattle Washington United States 98104
    500 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    501 Group Health Central Hospital Seattle Washington United States 98112
    502 Swedish Cancer Institute at Swedish Medical Center - First Hill Campus Seattle Washington United States 98122-4307
    503 Polyclinic First Hill Seattle Washington United States 98122
    504 University Cancer Center at University of Washington Medical Center Seattle Washington United States 98195
    505 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    506 Rockwood Clinic Cancer Treatment Center Spokane Washington United States 99204-2967
    507 Evergreen Hematology and Oncology, PS Spokane Washington United States 99218
    508 Franciscan Cancer Center at St. Joseph Medical Center Tacoma Washington United States 98405-3004
    509 Allenmore Hospital Tacoma Washington United States 98405
    510 CCOP - Northwest Tacoma Washington United States 98405
    511 MultiCare Regional Cancer Center at Tacoma General Hospital Tacoma Washington United States 98405
    512 St. Clare Hospital Tacoma Washington United States 98499
    513 Southwest Washington Medical Center Cancer Center Vancouver Washington United States 98668
    514 Wenatchee Valley Medical Center Wenatchee Washington United States 98801-2028
    515 West Virginia University Health Sciences Center - Charleston Charleston West Virginia United States 25304
    516 Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital Parkersburg West Virginia United States 26102
    517 Schiffler Cancer Center at Wheeling Hospital Wheeling West Virginia United States 26003
    518 Langlade Memorial Hospital Antigo Wisconsin United States 54409
    519 Fox Valley Hematology and Oncology - East Grant Street Appleton Wisconsin United States 54911-3496
    520 Marshfield Clinic - Chippewa Center Chippewa Falls Wisconsin United States 54729
    521 Marshfield Clinic Cancer Care at Regional Cancer Center Eau Claire Wisconsin United States 54701
    522 Vince Lombardi Cancer Center at Aurora Lakeland Medical Center - Elkhorn Elkhorn Wisconsin United States 53121
    523 Oncology Alliance - Franklin Franklin Wisconsin United States 53132
    524 Oncology Alliance, SC - Milwaukee - East Glendale Wisconsin United States 53212-1038
    525 Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center Green Bay Wisconsin United States 54301-3526
    526 Green Bay Oncology, Limited at St. Mary's Hospital Green Bay Wisconsin United States 54303
    527 St. Mary's Hospital Medical Center - Green Bay Green Bay Wisconsin United States 54303
    528 St. Vincent Hospital Regional Cancer Center Green Bay Wisconsin United States 54307-3508
    529 UW Cancer Center Johnson Creek Johnson Creek Wisconsin United States 53038
    530 Oncology Alliance - Kenosha South Kenosha Wisconsin United States 53143
    531 Gundersen Lutheran Center for Cancer and Blood La Crosse Wisconsin United States 54601
    532 University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison Wisconsin United States 53792-6164
    533 Holy Family Memorial Medical Center Cancer Care Center Manitowoc Wisconsin United States 54221-1450
    534 Bay Area Cancer Care Center at Bay Area Medical Center Marinette Wisconsin United States 54143
    535 Marshfield Clinic - Marshfield Center Marshfield Wisconsin United States 54449
    536 Saint Joseph's Hospital Marshfield Wisconsin United States 54449
    537 Medical Consultants, Limited Milwaukee Wisconsin United States 53215
    538 Oncology Alliance, SC - Milwaukee - South Milwaukee Wisconsin United States 53215
    539 Froedtert Hospital and Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    540 Medical College of Wisconsin Cancer Center Milwaukee Wisconsin United States 53226
    541 Marshfield Clinic - Lakeland Center Minocqua Wisconsin United States 54548
    542 Green Bay Oncology, Limited - Oconto Falls Oconto Falls Wisconsin United States 54154
    543 Ministry Medical Group at Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    544 Marshfield Clinic - Indianhead Center Rice Lake Wisconsin United States 54868
    545 Saint Michael's Hospital Cancer Center Stevens Point Wisconsin United States 54481
    546 Green Bay Oncology, Limited - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    547 Marshfield Clinic - Wausau Center Wausau Wisconsin United States 54401
    548 University of Wisconcin Cancer Center at Aspirus Wausau Hospital Wausau Wisconsin United States 54401
    549 Oncology Alliance, SC - Milwaukee - West Wauwatosa Wisconsin United States 53226
    550 Marshfield Clinic - Weston Center Weston Wisconsin United States 54476
    551 Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin United States 54494
    552 Riverview UW Cancer Center at Riverview Hospital Wisconsin Rapids Wisconsin United States 54494
    553 Rocky Mountain Oncology Casper Wyoming United States 82609
    554 Welch Cancer Center at Sheridan Memorial Hospital Sheridan Wyoming United States 82801

    Sponsors and Collaborators

    • Southwest Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: David I. Quinn, MD, University of Southern California
    • Study Chair: Maha Hadi A. Hussain, MD, University of Michigan Rogel Cancer Center
    • Study Chair: Primo N. Lara, MD, University of California, Davis
    • Study Chair: Mark Garzotto, MD, Portland VA Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00134056
    Other Study ID Numbers:
    • CDR0000439434
    • S0421
    • U10CA032102
    First Posted:
    Aug 24, 2005
    Last Update Posted:
    Oct 27, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Southwest Oncology Group
    adenocarcinoma of the prostate
    stage IV prostate cancer
    recurrent prostate cancer
    bone metastases
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Prednisone
    Docetaxel
    Atrasentan

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I: Placebo Arm II: Atrasentan
    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
    Period Title: Randomization
    STARTED 496 500
    COMPLETED 169 185
    NOT COMPLETED 327 315

    Baseline Characteristics

    Arm/Group Title Arm I: Placebo Arm II: Atrasentan Total
    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 Participants 496 498 994
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    69
    69
    69
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    496
    100%
    498
    100%
    994
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    20
    4%
    21
    4.2%
    41
    4.1%
    Not Hispanic or Latino
    476
    96%
    477
    95.8%
    953
    95.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of 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%
    Unknown
    14
    2.8%
    10
    2%
    24
    2.4%
    Serum PSA (ug/L) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ug/L]
    67.7
    79.0
    72.7
    Type of Progression at study entry (Count of 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 (Count of Participants)
    Count of Participants [Participants]
    305
    61.5%
    304
    61%
    609
    61.3%
    Brief Pain Inventory, worst pain (Count of Participants)
    >= 4
    213
    42.9%
    210
    42.2%
    423
    42.6%
    <4
    283
    57.1%
    288
    57.8%
    571
    57.4%
    Metastases (Count of 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%
    101
    20.3%
    195
    19.6%
    Extraskeletal
    48
    9.7%
    45
    9%
    93
    9.4%
    Previous prostatectomy (Count of Participants)
    Count of Participants [Participants]
    145
    29.2%
    168
    33.7%
    313
    31.5%
    Performance status (Count of Participants)
    2-3
    39
    7.9%
    36
    7.2%
    75
    7.5%
    0-1
    457
    92.1%
    462
    92.8%
    919
    92.5%
    Gleason score (Count of Participants)
    5-6
    49
    9.9%
    52
    10.4%
    101
    10.2%
    7
    137
    27.6%
    141
    28.3%
    278
    28%
    8-10
    272
    54.8%
    275
    55.2%
    547
    55%
    Missing
    38
    7.7%
    30
    6%
    68
    6.8%

    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. 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 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
    Measure Participants 496 498
    Median (95% Confidence Interval) [months]
    17.6
    17.8
    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
    Statistical Test of Hypothesis p-Value 0.64
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.90 to 1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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 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 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
    Measure Participants 496 498
    Median (95% Confidence Interval) [months]
    9.1
    9.2
    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
    Statistical Test of Hypothesis p-Value 0.81
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.89 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Compare Pain Progression Between the Two Study Arms.
    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 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
    Measure Participants 416 408
    Count of Participants [Participants]
    59
    11.9%
    41
    8.2%
    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 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 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.
    Measure Participants 486 492
    ALT, SGPT (serum glutamic pyruvic transaminase)
    2
    0.4%
    2
    0.4%
    AST, SGOT
    2
    0.4%
    4
    0.8%
    Adult respiratory distress syndrome (ARDS)
    3
    0.6%
    0
    0%
    Albumin, serum-low (hypoalbuminemia)
    3
    0.6%
    0
    0%
    Alkaline phosphatase
    4
    0.8%
    6
    1.2%
    Allergic reaction/hypersensitivity
    5
    1%
    6
    1.2%
    Allergy/Immunology-Other (Specify)
    0
    0%
    1
    0.2%
    Amylase
    0
    0%
    1
    0.2%
    Anorexia
    5
    1%
    5
    1%
    Arthritis (non-septic)
    1
    0.2%
    0
    0%
    Aspiration
    0
    0%
    1
    0.2%
    Auditory/Ear-Other (Specify)
    1
    0.2%
    0
    0%
    Bilirubin (hyperbilirubinemia)
    0
    0%
    1
    0.2%
    Blood/Bone Marrow-Other (Specify)
    2
    0.4%
    2
    0.4%
    CNS cerebrovascular ischemia
    0
    0%
    1
    0.2%
    CPK (creatine phosphokinase)
    2
    0.4%
    0
    0%
    Calcium, serum-low (hypocalcemia)
    7
    1.4%
    1
    0.2%
    Cardiac Arrhythmia-Other (Specify)
    2
    0.4%
    0
    0%
    Cardiac General-Other (Specify)
    1
    0.2%
    1
    0.2%
    Cardiac troponin I (cTnI)
    2
    0.4%
    1
    0.2%
    Cardiac troponin T (cTnT)
    1
    0.2%
    0
    0%
    Cardiac-ischemia/infarction
    2
    0.4%
    1
    0.2%
    Conduction abnormality NOS
    1
    0.2%
    0
    0%
    Confusion
    1
    0.2%
    0
    0%
    Constipation
    3
    0.6%
    4
    0.8%
    Cough
    1
    0.2%
    2
    0.4%
    Creatinine
    4
    0.8%
    1
    0.2%
    Dehydration
    9
    1.8%
    8
    1.6%
    Diarrhea
    10
    2%
    7
    1.4%
    Dizziness
    3
    0.6%
    1
    0.2%
    Dry mouth/salivary gland (xerostomia)
    1
    0.2%
    0
    0%
    Dysphagia (difficulty swallowing)
    1
    0.2%
    1
    0.2%
    Dyspnea (shortness of breath)
    38
    7.7%
    17
    3.4%
    Edema: head and neck
    0
    0%
    1
    0.2%
    Edema: limb
    16
    3.2%
    2
    0.4%
    Edema: trunk/genital
    1
    0.2%
    0
    0%
    Erectile dysfunction
    2
    0.4%
    0
    0%
    Esophagitis
    0
    0%
    1
    0.2%
    Fatigue (asthenia, lethargy, malaise)
    60
    12.1%
    40
    8%
    Febrile neutropenia
    8
    1.6%
    20
    4%
    Fever in absence of neutropenia, ANC lt1.0x10e9/L
    1
    0.2%
    2
    0.4%
    Fracture
    1
    0.2%
    0
    0%
    Glucose, serum-high (hyperglycemia)
    20
    4%
    24
    4.8%
    Glucose, serum-low (hypoglycemia)
    1
    0.2%
    0
    0%
    Heartburn/dyspepsia
    1
    0.2%
    1
    0.2%
    Hemoglobin
    47
    9.5%
    22
    4.4%
    Hemolysis
    1
    0.2%
    0
    0%
    Hemorrhage, Respiratory tract NOS
    0
    0%
    1
    0.2%
    Hemorrhage, GI - Rectum
    1
    0.2%
    0
    0%
    Hemorrhage, GI - Stomach
    1
    0.2%
    0
    0%
    Hemorrhage, GI - Upper GI NOS
    0
    0%
    1
    0.2%
    Hemorrhage, GU - Bladder
    0
    0%
    1
    0.2%
    Hemorrhage/Bleeding-Other (Specify)
    2
    0.4%
    1
    0.2%
    Hemorrhoids
    0
    0%
    2
    0.4%
    Hot flashes/flushes
    2
    0.4%
    1
    0.2%
    Hypertension
    2
    0.4%
    2
    0.4%
    Hypotension
    9
    1.8%
    3
    0.6%
    Hypoxia
    10
    2%
    3
    0.6%
    INR (of prothrombin time)
    3
    0.6%
    1
    0.2%
    Induration/fibrosis (skin and subcutaneous tissue)
    1
    0.2%
    0
    0%
    Inf (clin/microbio) w/Gr 3-4 neuts - Bladder
    1
    0.2%
    2
    0.4%
    Inf (clin/microbio) w/Gr 3-4 neuts - Blood
    2
    0.4%
    0
    0%
    Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus
    0
    0%
    1
    0.2%
    Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus
    0
    0%
    1
    0.2%
    Inf (clin/microbio) w/Gr 3-4 neuts - Lung
    11
    2.2%
    6
    1.2%
    Inf (clin/microbio) w/Gr 3-4 neuts - Nerve-periph
    1
    0.2%
    0
    0%
    Inf (clin/microbio) w/Gr 3-4 neuts - Skin
    1
    0.2%
    2
    0.4%
    Inf (clin/microbio) w/Gr 3-4 neuts - Soft tissue
    1
    0.2%
    0
    0%
    Inf (clin/microbio) w/Gr 3-4 neuts - UTI
    4
    0.8%
    3
    0.6%
    Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway
    0
    0%
    2
    0.4%
    Inf w/normal ANC or Gr 1-2 neutrophils - Blood
    2
    0.4%
    1
    0.2%
    Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus
    1
    0.2%
    1
    0.2%
    Inf w/normal ANC or Gr 1-2 neutrophils - Colon
    1
    0.2%
    0
    0%
    Inf w/normal ANC or Gr 1-2 neutrophils - Lung
    1
    0.2%
    5
    1%
    Inf w/normal ANC or Gr 1-2 neutrophils - Muscle
    1
    0.2%
    0
    0%
    Inf w/normal ANC or Gr 1-2 neutrophils - Scrotum
    0
    0%
    1
    0.2%
    Inf w/normal ANC or Gr 1-2 neutrophils - Sinus
    1
    0.2%
    0
    0%
    Inf w/normal ANC or Gr 1-2 neutrophils - Skin
    1
    0.2%
    2
    0.4%
    Inf w/normal ANC or Gr 1-2 neutrophils - Stomach
    1
    0.2%
    0
    0%
    Inf w/normal ANC or Gr 1-2 neutrophils - Trachea
    1
    0.2%
    0
    0%
    Inf w/normal ANC or Gr 1-2 neutrophils - UTI
    0
    0%
    1
    0.2%
    Inf w/normal ANC or Gr 1-2 neutrophils - Ungual
    0
    0%
    1
    0.2%
    Inf w/unknown ANC - Middle ear (otitis media)
    0
    0%
    1
    0.2%
    Inf w/unknown ANC - Upper aerodigestive NOS
    0
    0%
    1
    0.2%
    Infection with unknown ANC - Blood
    0
    0%
    1
    0.2%
    Infection with unknown ANC - Lung (pneumonia)
    3
    0.6%
    0
    0%
    Infection with unknown ANC - Upper airway NOS
    0
    0%
    1
    0.2%
    Infection with unknown ANC - Urinary tract NOS
    1
    0.2%
    1
    0.2%
    Infection-Other (Specify)
    4
    0.8%
    3
    0.6%
    Insomnia
    1
    0.2%
    1
    0.2%
    Left ventricular diastolic dysfunction
    1
    0.2%
    0
    0%
    Left ventricular systolic dysfunction
    3
    0.6%
    2
    0.4%
    Leukocytes (total WBC)
    101
    20.4%
    98
    19.7%
    Lipase
    0
    0%
    1
    0.2%
    Lymphopenia
    30
    6%
    32
    6.4%
    Magnesium, serum-high (hypermagnesemia)
    1
    0.2%
    0
    0%
    Metabolic/Laboratory-Other (Specify)
    0
    0%
    2
    0.4%
    Mood alteration - agitation
    1
    0.2%
    0
    0%
    Mood alteration - depression
    1
    0.2%
    0
    0%
    Mucositis/stomatitis (clinical exam) - Oral cavity
    2
    0.4%
    2
    0.4%
    Mucositis/stomatitis (clinical exam) - Pharynx
    1
    0.2%
    0
    0%
    Mucositis/stomatitis (clinical exam) - Stomach
    1
    0.2%
    0
    0%
    Mucositis/stomatitis (functional/symp) - Esophagus
    0
    0%
    1
    0.2%
    Mucositis/stomatitis (functional/symp) - Oral cav
    3
    0.6%
    3
    0.6%
    Mucositis/stomatitis (functional/symp) - Pharynx
    0
    0%
    1
    0.2%
    Mucositis/stomatitis (functional/symp) - Rectum
    0
    0%
    1
    0.2%
    Muscle weakness, not d/t neuropathy - Extrem-lower
    2
    0.4%
    1
    0.2%
    Muscle weakness, not d/t neuropathy - body/general
    11
    2.2%
    8
    1.6%
    Myocarditis
    1
    0.2%
    0
    0%
    Nail changes
    0
    0%
    1
    0.2%
    Nasal cavity/paranasal sinus reactions
    2
    0.4%
    0
    0%
    Nausea
    11
    2.2%
    5
    1%
    Neuropathy: motor
    7
    1.4%
    6
    1.2%
    Neuropathy: sensory
    10
    2%
    11
    2.2%
    Neutrophils/granulocytes (ANC/AGC)
    140
    28.2%
    154
    30.9%
    Opportunistic inf associated w/gt=Gr 2 lymphopenia
    1
    0.2%
    1
    0.2%
    PTT (Partial thromboplastin time)
    1
    0.2%
    0
    0%
    Pain - Abdomen NOS
    4
    0.8%
    0
    0%
    Pain - Back
    1
    0.2%
    2
    0.4%
    Pain - Bone
    5
    1%
    8
    1.6%
    Pain - Chest wall
    0
    0%
    1
    0.2%
    Pain - Chest/thorax NOS
    1
    0.2%
    0
    0%
    Pain - Extremity-limb
    1
    0.2%
    1
    0.2%
    Pain - Joint
    2
    0.4%
    2
    0.4%
    Pain - Muscle
    8
    1.6%
    3
    0.6%
    Pain - Neuralgia/peripheral nerve
    1
    0.2%
    1
    0.2%
    Pain - Pelvis
    0
    0%
    1
    0.2%
    Pain-Other (Specify)
    0
    0%
    1
    0.2%
    Phosphate, serum-low (hypophosphatemia)
    3
    0.6%
    0
    0%
    Platelets
    7
    1.4%
    4
    0.8%
    Pneumonitis/pulmonary infiltrates
    7
    1.4%
    0
    0%
    Pneumothorax
    1
    0.2%
    0
    0%
    Potassium, serum-high (hyperkalemia)
    2
    0.4%
    1
    0.2%
    Potassium, serum-low (hypokalemia)
    11
    2.2%
    2
    0.4%
    Pulmonary/Upper Respiratory-Other (Specify)
    0
    0%
    1
    0.2%
    Rash: hand-foot skin reaction
    1
    0.2%
    0
    0%
    Renal failure
    4
    0.8%
    2
    0.4%
    Renal/Genitourinary-Other (Specify)
    1
    0.2%
    0
    0%
    Right ventricular dysfunction (cor pulmonale)
    0
    0%
    1
    0.2%
    SVT and nodal arrhythmia - Atrial fibrillation
    3
    0.6%
    2
    0.4%
    SVT and nodal arrhythmia - Atrial flutter
    1
    0.2%
    1
    0.2%
    SVT and nodal arrhythmia - Sinus tachycardia
    0
    0%
    1
    0.2%
    Sodium, serum-low (hyponatremia)
    8
    1.6%
    3
    0.6%
    Somnolence/depressed level of consciousness
    1
    0.2%
    0
    0%
    Speech impairment (e.g., dysphasia or aphasia)
    0
    0%
    1
    0.2%
    Sudden death
    2
    0.4%
    0
    0%
    Syncope (fainting)
    3
    0.6%
    1
    0.2%
    Thrombosis/embolism (vascular access-related)
    0
    0%
    1
    0.2%
    Thrombosis/thrombus/embolism
    9
    1.8%
    11
    2.2%
    Vasovagal episode
    0
    0%
    2
    0.4%
    Vomiting
    8
    1.6%
    7
    1.4%
    Watery eye (epiphora, tearing)
    0
    0%
    1
    0.2%
    Weight gain
    0
    0%
    1
    0.2%
    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 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 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
    Measure Participants 496 498
    Count of Participants [Participants]
    243
    49%
    249
    50%
    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 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 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
    Measure Participants 225 225
    Partial response (confirmed)
    31
    6.3%
    32
    6.4%
    Complete response
    0
    0%
    0
    0%
    No response
    194
    39.1%
    193
    38.8%
    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 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 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
    Measure Participants 274 260
    Count of Participants [Participants]
    75
    15.1%
    83
    16.7%
    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 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 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
    Measure Participants 487 484
    Count of Participants [Participants]
    118
    23.8%
    139
    27.9%

    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 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 (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Arm I: Placebo Arm II: Atrasentan
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 172/486 (35.4%) 153/492 (31.1%)
    Blood and lymphatic system disorders
    DIC (disseminated intravascular coagulation) 1/486 (0.2%) 0/492 (0%)
    Febrile neutropenia 9/486 (1.9%) 9/492 (1.8%)
    Hemoglobin 10/486 (2.1%) 5/492 (1%)
    Cardiac disorders
    Cardiac General-Other 3/486 (0.6%) 0/492 (0%)
    Cardiac-ischemia/infarction 7/486 (1.4%) 2/492 (0.4%)
    Cardiopulmonary arrest, cause unknown (non-fatal) 0/486 (0%) 2/492 (0.4%)
    Left ventricular diastolic dysfunction 2/486 (0.4%) 0/492 (0%)
    Left ventricular systolic dysfunction 1/486 (0.2%) 2/492 (0.4%)
    Myocarditis 1/486 (0.2%) 0/492 (0%)
    Right ventricular dysfunction (cor pulmonale) 0/486 (0%) 1/492 (0.2%)
    SVT and nodal arrhythmia - Atrial fibrillation 8/486 (1.6%) 3/492 (0.6%)
    SVT and nodal arrhythmia - Atrial flutter 3/486 (0.6%) 2/492 (0.4%)
    SVT and nodal arrhythmia - Sinus bradycardia 1/486 (0.2%) 0/492 (0%)
    Ventricular arrhythmia - PVCs 1/486 (0.2%) 0/492 (0%)
    Ventricular arrhythmia - Ventricular fibrillation 0/486 (0%) 1/492 (0.2%)
    Ventricular arrhythmia - Ventricular tachycardia 1/486 (0.2%) 0/492 (0%)
    Ear and labyrinth disorders
    Otitis, middle ear (non-infectious) 1/486 (0.2%) 0/492 (0%)
    Eye disorders
    Vision-blurred vision 0/486 (0%) 1/492 (0.2%)
    Gastrointestinal disorders
    Colitis 1/486 (0.2%) 0/492 (0%)
    Constipation 1/486 (0.2%) 3/492 (0.6%)
    Diarrhea 6/486 (1.2%) 4/492 (0.8%)
    Distention/bloating, abdominal 1/486 (0.2%) 0/492 (0%)
    Dry mouth/salivary gland (xerostomia) 1/486 (0.2%) 0/492 (0%)
    Dysphagia (difficulty swallowing) 1/486 (0.2%) 1/492 (0.2%)
    Esophagitis 0/486 (0%) 1/492 (0.2%)
    Gastrointestinal-Other 1/486 (0.2%) 0/492 (0%)
    Hemorrhage, GI - Abdomen NOS 1/486 (0.2%) 0/492 (0%)
    Hemorrhage, GI - Colon 1/486 (0.2%) 1/492 (0.2%)
    Hemorrhage, GI - Duodenum 2/486 (0.4%) 2/492 (0.4%)
    Hemorrhage, GI - Lower GI NOS 0/486 (0%) 1/492 (0.2%)
    Hemorrhage, GI - Rectum 3/486 (0.6%) 2/492 (0.4%)
    Hemorrhage, GI - Stomach 1/486 (0.2%) 0/492 (0%)
    Hemorrhage, GI - Upper GI NOS 1/486 (0.2%) 3/492 (0.6%)
    Ileus, GI (functional obstruction of bowel) 1/486 (0.2%) 0/492 (0%)
    Mucositis/stomatitis (clinical exam) - Esophagus 0/486 (0%) 1/492 (0.2%)
    Mucositis/stomatitis (clinical exam) - Oral cavity 2/486 (0.4%) 1/492 (0.2%)
    Nausea 5/486 (1%) 6/492 (1.2%)
    Obstruction, GI - Colon 0/486 (0%) 1/492 (0.2%)
    Obstruction, GI - Small bowel NOS 1/486 (0.2%) 3/492 (0.6%)
    Pain - Abdomen NOS 7/486 (1.4%) 5/492 (1%)
    Perforation, GI - Colon 1/486 (0.2%) 0/492 (0%)
    Perforation, GI - Duodenum 0/486 (0%) 1/492 (0.2%)
    Perforation, GI - Small bowel NOS 0/486 (0%) 1/492 (0.2%)
    Proctitis 0/486 (0%) 1/492 (0.2%)
    Stricture/stenosis (including anastomotic), GI - A 1/486 (0.2%) 0/492 (0%)
    Ulcer, GI - Duodenum 2/486 (0.4%) 2/492 (0.4%)
    Ulcer, GI - Rectum 1/486 (0.2%) 0/492 (0%)
    Ulcer, GI - Stomach 1/486 (0.2%) 1/492 (0.2%)
    Vomiting 6/486 (1.2%) 9/492 (1.8%)
    General disorders
    Death - Multi-organ failure 3/486 (0.6%) 0/492 (0%)
    Death not associated with CTCAE term - Death NOS 4/486 (0.8%) 5/492 (1%)
    Edema: head and neck 0/486 (0%) 1/492 (0.2%)
    Edema: limb 4/486 (0.8%) 0/492 (0%)
    Fatigue (asthenia, lethargy, malaise) 14/486 (2.9%) 6/492 (1.2%)
    Fever in absence of neutropenia, ANC lt1.0x10e9/L 0/486 (0%) 1/492 (0.2%)
    Pain - Chest/thorax NOS 2/486 (0.4%) 2/492 (0.4%)
    Pain - Pain NOS 0/486 (0%) 1/492 (0.2%)
    Pain-Other 3/486 (0.6%) 1/492 (0.2%)
    Sudden death 3/486 (0.6%) 2/492 (0.4%)
    Infections and infestations
    Inf (clin/microbio) w/Gr 3-4 neuts - Appendix 0/486 (0%) 1/492 (0.2%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Bladder 1/486 (0.2%) 2/492 (0.4%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Blood 4/486 (0.8%) 3/492 (0.6%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Colon 1/486 (0.2%) 0/492 (0%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Eye NOS 1/486 (0.2%) 0/492 (0%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Lung 14/486 (2.9%) 8/492 (1.6%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Nerve-periph 1/486 (0.2%) 0/492 (0%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Nose 1/486 (0.2%) 0/492 (0%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Pharynx 1/486 (0.2%) 0/492 (0%)
    Inf (clin/microbio) w/Gr 3-4 neuts - UTI 7/486 (1.4%) 6/492 (1.2%)
    Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway 0/486 (0%) 1/492 (0.2%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Ab NOS 1/486 (0.2%) 0/492 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Bladder 0/486 (0%) 1/492 (0.2%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Blood 5/486 (1%) 0/492 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus 0/486 (0%) 1/492 (0.2%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Catheter 2/486 (0.4%) 0/492 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Colon 1/486 (0.2%) 0/492 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Liver 1/486 (0.2%) 0/492 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Lung 12/486 (2.5%) 9/492 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Mid ear 0/486 (0%) 1/492 (0.2%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Muscle 1/486 (0.2%) 0/492 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Scrotum 0/486 (0%) 1/492 (0.2%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Skin 3/486 (0.6%) 2/492 (0.4%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Trachea 1/486 (0.2%) 0/492 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - UTI 3/486 (0.6%) 4/492 (0.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Wound 0/486 (0%) 2/492 (0.4%)
    Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-peri 0/486 (0%) 1/492 (0.2%)
    Inf w/unknown ANC - Middle ear (otitis media) 0/486 (0%) 1/492 (0.2%)
    Inf w/unknown ANC - Upper aerodigestive NOS 0/486 (0%) 1/492 (0.2%)
    Infection (documented clinically or microbiologica 2/486 (0.4%) 0/492 (0%)
    Infection with unknown ANC - Blood 0/486 (0%) 1/492 (0.2%)
    Infection with unknown ANC - Lung (pneumonia) 1/486 (0.2%) 0/492 (0%)
    Infection with unknown ANC - Rectum 0/486 (0%) 1/492 (0.2%)
    Infection with unknown ANC - Upper airway NOS 0/486 (0%) 1/492 (0.2%)
    Infection with unknown ANC - Urinary tract NOS 0/486 (0%) 1/492 (0.2%)
    Infection with unknown ANC - Wound 1/486 (0.2%) 0/492 (0%)
    Infection-Other 1/486 (0.2%) 1/492 (0.2%)
    Perforation, GI - Appendix 0/486 (0%) 3/492 (0.6%)
    Injury, poisoning and procedural complications
    Fracture 5/486 (1%) 3/492 (0.6%)
    Thrombosis/embolism (vascular access-related) 0/486 (0%) 1/492 (0.2%)
    Investigations
    ALT, SGPT (serum glutamic pyruvic transaminase) 0/486 (0%) 1/492 (0.2%)
    AST, SGOT 1/486 (0.2%) 1/492 (0.2%)
    Alkaline phosphatase 1/486 (0.2%) 1/492 (0.2%)
    Bilirubin (hyperbilirubinemia) 1/486 (0.2%) 0/492 (0%)
    CPK (creatine phosphokinase) 1/486 (0.2%) 0/492 (0%)
    Cardiac troponin I (cTnI) 5/486 (1%) 1/492 (0.2%)
    Cardiac troponin T (cTnT) 1/486 (0.2%) 0/492 (0%)
    Creatinine 6/486 (1.2%) 4/492 (0.8%)
    Fibrinogen 1/486 (0.2%) 0/492 (0%)
    INR (of prothrombin time) 1/486 (0.2%) 1/492 (0.2%)
    Leukocytes (total WBC) 8/486 (1.6%) 8/492 (1.6%)
    Lymphopenia 1/486 (0.2%) 1/492 (0.2%)
    Metabolic/Laboratory-Other 0/486 (0%) 1/492 (0.2%)
    Neutrophils/granulocytes (ANC/AGC) 15/486 (3.1%) 11/492 (2.2%)
    Platelets 1/486 (0.2%) 0/492 (0%)
    Prolonged QTc interval 1/486 (0.2%) 0/492 (0%)
    Weight loss 1/486 (0.2%) 0/492 (0%)
    Metabolism and nutrition disorders
    Acidosis (metabolic or respiratory) 1/486 (0.2%) 1/492 (0.2%)
    Albumin, serum-low (hypoalbuminemia) 2/486 (0.4%) 1/492 (0.2%)
    Anorexia 4/486 (0.8%) 4/492 (0.8%)
    Calcium, serum-low (hypocalcemia) 7/486 (1.4%) 0/492 (0%)
    Dehydration 13/486 (2.7%) 7/492 (1.4%)
    Glucose, serum-high (hyperglycemia) 5/486 (1%) 7/492 (1.4%)
    Glucose, serum-low (hypoglycemia) 2/486 (0.4%) 0/492 (0%)
    Magnesium, serum-high (hypermagnesemia) 1/486 (0.2%) 0/492 (0%)
    Phosphate, serum-low (hypophosphatemia) 1/486 (0.2%) 0/492 (0%)
    Potassium, serum-high (hyperkalemia) 0/486 (0%) 1/492 (0.2%)
    Potassium, serum-low (hypokalemia) 3/486 (0.6%) 0/492 (0%)
    Sodium, serum-low (hyponatremia) 3/486 (0.6%) 4/492 (0.8%)
    Musculoskeletal and connective tissue disorders
    Joint-effusion 1/486 (0.2%) 0/492 (0%)
    Muscle weakness, not d/t neuropathy - Extrem-lower 2/486 (0.4%) 2/492 (0.4%)
    Muscle weakness, not d/t neuropathy - body/general 4/486 (0.8%) 3/492 (0.6%)
    Musculoskeletal/Soft Tissue-Other 1/486 (0.2%) 0/492 (0%)
    Osteonecrosis (avascular necrosis) 0/486 (0%) 1/492 (0.2%)
    Pain - Back 3/486 (0.6%) 3/492 (0.6%)
    Pain - Bone 5/486 (1%) 2/492 (0.4%)
    Pain - Chest wall 0/486 (0%) 1/492 (0.2%)
    Pain - Extremity-limb 2/486 (0.4%) 4/492 (0.8%)
    Pain - Joint 1/486 (0.2%) 0/492 (0%)
    Pain - Muscle 1/486 (0.2%) 0/492 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Death - Disease progression NOS 10/486 (2.1%) 11/492 (2.2%)
    Pain - Tumor pain 1/486 (0.2%) 0/492 (0%)
    Nervous system disorders
    CNS cerebrovascular ischemia 0/486 (0%) 4/492 (0.8%)
    Dizziness 1/486 (0.2%) 3/492 (0.6%)
    Hemorrhage, CNS 1/486 (0.2%) 1/492 (0.2%)
    Mental status 0/486 (0%) 1/492 (0.2%)
    Neurology-Other 0/486 (0%) 1/492 (0.2%)
    Neuropathy: CN III Pupil, eyelid, xtra ocular mvmt 0/486 (0%) 1/492 (0.2%)
    Neuropathy: CN VII Motor-face; Sensory-taste 0/486 (0%) 1/492 (0.2%)
    Neuropathy: cranial - CN VI Lateral deviation of e 0/486 (0%) 1/492 (0.2%)
    Neuropathy: motor 1/486 (0.2%) 2/492 (0.4%)
    Pain - Head/headache 0/486 (0%) 1/492 (0.2%)
    Somnolence/depressed level of consciousness 3/486 (0.6%) 0/492 (0%)
    Speech impairment (e.g., dysphasia or aphasia) 0/486 (0%) 1/492 (0.2%)
    Syncope (fainting) 4/486 (0.8%) 0/492 (0%)
    Taste alteration (dysgeusia) 1/486 (0.2%) 0/492 (0%)
    Vasovagal episode 0/486 (0%) 1/492 (0.2%)
    Psychiatric disorders
    Confusion 4/486 (0.8%) 4/492 (0.8%)
    Mood alteration - depression 0/486 (0%) 2/492 (0.4%)
    Personality/behavioral 0/486 (0%) 1/492 (0.2%)
    Psychosis (hallucinations/delusions) 0/486 (0%) 1/492 (0.2%)
    Renal and urinary disorders
    Hemorrhage, GU - Bladder 0/486 (0%) 2/492 (0.4%)
    Hemorrhage, GU - Urinary NOS 1/486 (0.2%) 1/492 (0.2%)
    Obstruction, GU - Ureter 0/486 (0%) 2/492 (0.4%)
    Obstruction, GU - Urethra 0/486 (0%) 1/492 (0.2%)
    Renal failure 8/486 (1.6%) 7/492 (1.4%)
    Renal/Genitourinary-Other 1/486 (0.2%) 0/492 (0%)
    Urinary retention (including neurogenic bladder) 3/486 (0.6%) 3/492 (0.6%)
    Reproductive system and breast disorders
    Pain - Testicle 0/486 (0%) 1/492 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome (ARDS) 2/486 (0.4%) 1/492 (0.2%)
    Aspiration 0/486 (0%) 1/492 (0.2%)
    Dyspnea (shortness of breath) 25/486 (5.1%) 9/492 (1.8%)
    Edema, larynx 0/486 (0%) 1/492 (0.2%)
    Hemorrhage, Respiratory tract NOS 0/486 (0%) 1/492 (0.2%)
    Hemorrhage, pulmonary/upper respiratory - Lung 1/486 (0.2%) 0/492 (0%)
    Hypoxia 10/486 (2.1%) 3/492 (0.6%)
    Pleural effusion (non-malignant) 2/486 (0.4%) 0/492 (0%)
    Pneumonitis/pulmonary infiltrates 7/486 (1.4%) 4/492 (0.8%)
    Pulmonary fibrosis (radiographic changes) 0/486 (0%) 1/492 (0.2%)
    Skin and subcutaneous tissue disorders
    Dermatology/Skin-Other 0/486 (0%) 1/492 (0.2%)
    Hyperpigmentation 1/486 (0.2%) 0/492 (0%)
    Induration/fibrosis (skin and subcutaneous tissue) 1/486 (0.2%) 0/492 (0%)
    Pain - Scalp 0/486 (0%) 1/492 (0.2%)
    Vascular disorders
    Hematoma 0/486 (0%) 1/492 (0.2%)
    Hypertension 2/486 (0.4%) 1/492 (0.2%)
    Hypotension 13/486 (2.7%) 7/492 (1.4%)
    Thrombosis/thrombus/embolism 12/486 (2.5%) 17/492 (3.5%)
    Other (Not Including Serious) Adverse Events
    Arm I: Placebo Arm II: Atrasentan
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 476/486 (97.9%) 475/492 (96.5%)
    Blood and lymphatic system disorders
    Hemoglobin 350/486 (72%) 331/492 (67.3%)
    Eye disorders
    Vision-blurred vision 26/486 (5.3%) 14/492 (2.8%)
    Watery eye (epiphora, tearing) 37/486 (7.6%) 41/492 (8.3%)
    Gastrointestinal disorders
    Constipation 185/486 (38.1%) 176/492 (35.8%)
    Diarrhea 143/486 (29.4%) 149/492 (30.3%)
    Dry mouth/salivary gland (xerostomia) 33/486 (6.8%) 23/492 (4.7%)
    Heartburn/dyspepsia 36/486 (7.4%) 43/492 (8.7%)
    Mucositis/stomatitis (clinical exam) - Oral cavity 39/486 (8%) 27/492 (5.5%)
    Mucositis/stomatitis (functional/symp) - Oral cav 30/486 (6.2%) 46/492 (9.3%)
    Nausea 201/486 (41.4%) 188/492 (38.2%)
    Pain - Abdomen NOS 29/486 (6%) 46/492 (9.3%)
    Vomiting 78/486 (16%) 62/492 (12.6%)
    General disorders
    Edema: limb 284/486 (58.4%) 178/492 (36.2%)
    Fatigue (asthenia, lethargy, malaise) 357/486 (73.5%) 346/492 (70.3%)
    Fever in absence of neutropenia, ANC lt1.0x10e9/L 43/486 (8.8%) 30/492 (6.1%)
    Pain-Other 32/486 (6.6%) 34/492 (6.9%)
    Injury, poisoning and procedural complications
    Bruising (in absence of Gr 3-4 thrombocytopenia) 27/486 (5.6%) 21/492 (4.3%)
    Investigations
    ALT, SGPT (serum glutamic pyruvic transaminase) 33/486 (6.8%) 36/492 (7.3%)
    AST, SGOT 71/486 (14.6%) 80/492 (16.3%)
    Alkaline phosphatase 106/486 (21.8%) 113/492 (23%)
    Creatinine 79/486 (16.3%) 71/492 (14.4%)
    Leukocytes (total WBC) 165/486 (34%) 165/492 (33.5%)
    Lymphopenia 76/486 (15.6%) 72/492 (14.6%)
    Metabolic/Laboratory-Other 23/486 (4.7%) 27/492 (5.5%)
    Neutrophils/granulocytes (ANC/AGC) 179/486 (36.8%) 180/492 (36.6%)
    Platelets 71/486 (14.6%) 47/492 (9.6%)
    Weight gain 49/486 (10.1%) 36/492 (7.3%)
    Weight loss 39/486 (8%) 36/492 (7.3%)
    Metabolism and nutrition disorders
    Albumin, serum-low (hypoalbuminemia) 91/486 (18.7%) 90/492 (18.3%)
    Anorexia 112/486 (23%) 106/492 (21.5%)
    Calcium, serum-low (hypocalcemia) 109/486 (22.4%) 75/492 (15.2%)
    Dehydration 27/486 (5.6%) 29/492 (5.9%)
    Glucose, serum-high (hyperglycemia) 191/486 (39.3%) 202/492 (41.1%)
    Potassium, serum-high (hyperkalemia) 36/486 (7.4%) 33/492 (6.7%)
    Potassium, serum-low (hypokalemia) 59/486 (12.1%) 47/492 (9.6%)
    Sodium, serum-low (hyponatremia) 75/486 (15.4%) 61/492 (12.4%)
    Musculoskeletal and connective tissue disorders
    Muscle weakness, not d/t neuropathy - body/general 39/486 (8%) 44/492 (8.9%)
    Pain - Back 85/486 (17.5%) 86/492 (17.5%)
    Pain - Bone 138/486 (28.4%) 156/492 (31.7%)
    Pain - Extremity-limb 41/486 (8.4%) 45/492 (9.1%)
    Pain - Joint 112/486 (23%) 119/492 (24.2%)
    Pain - Muscle 119/486 (24.5%) 104/492 (21.1%)
    Nervous system disorders
    Dizziness 91/486 (18.7%) 96/492 (19.5%)
    Neuropathy: motor 25/486 (5.1%) 43/492 (8.7%)
    Neuropathy: sensory 202/486 (41.6%) 223/492 (45.3%)
    Pain - Head/headache 70/486 (14.4%) 45/492 (9.1%)
    Taste alteration (dysgeusia) 158/486 (32.5%) 132/492 (26.8%)
    Psychiatric disorders
    Insomnia 74/486 (15.2%) 80/492 (16.3%)
    Mood alteration - anxiety 20/486 (4.1%) 27/492 (5.5%)
    Mood alteration - depression 37/486 (7.6%) 28/492 (5.7%)
    Renal and urinary disorders
    Urinary frequency/urgency 48/486 (9.9%) 58/492 (11.8%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 78/486 (16%) 50/492 (10.2%)
    Cough 92/486 (18.9%) 80/492 (16.3%)
    Dyspnea (shortness of breath) 197/486 (40.5%) 156/492 (31.7%)
    Hemorrhage, pulmonary/upper respiratory - Nose 17/486 (3.5%) 29/492 (5.9%)
    Nasal cavity/paranasal sinus reactions 40/486 (8.2%) 30/492 (6.1%)
    Skin and subcutaneous tissue disorders
    Dry skin 28/486 (5.8%) 33/492 (6.7%)
    Hair loss/Alopecia (scalp or body) 201/486 (41.4%) 192/492 (39%)
    Nail changes 97/486 (20%) 149/492 (30.3%)
    Rash/desquamation 45/486 (9.3%) 70/492 (14.2%)
    Vascular disorders
    Hot flashes/flushes 65/486 (13.4%) 71/492 (14.4%)
    Hypertension 14/486 (2.9%) 35/492 (7.1%)
    Hypotension 69/486 (14.2%) 42/492 (8.5%)

    Limitations/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

    Name/Title Dr. David I Quinn
    Organization University of Southern California Norris Comprehensive Cancer Center
    Phone 3238653956
    Email diquinn@med.usc.edu
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00134056
    Other Study ID Numbers:
    • CDR0000439434
    • S0421
    • U10CA032102
    First Posted:
    Aug 24, 2005
    Last Update Posted:
    Oct 27, 2021
    Last Verified:
    Oct 1, 2021