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Last Modified: 7/8/2008     First Published: 8/19/2005  
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Phase III Randomized Study of Docetaxel and Prednisone With Versus Without Atrasentan in Patients With Hormone-Refractory Stage IV Prostate Cancer and Bone Metastases

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase
Type
Status
Age
Sponsor
Protocol IDs

Phase III


Treatment


Active


18 and over


NCI


SWOG-S0421
NCT00134056, S0421

Objectives

Primary

  1. 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

  1. Compare pain progression of patients treated with these regimens.
  2. Compare the qualitative and quantitative toxicity of these regimens in these patients.
  3. Compare the quality of life, in terms of palliation of metastatic bone pain and improvement in functional status, of patients treated with these regimens.
  4. Compare prostate-specific antigen (PSA) response rates in patients treated with these regimens.
  5. Compare objective response in patients with measurable disease treated with these regimens.
  6. 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.
  7. Correlate PSA progression with clinical progression and death in patients treated with these regimens.

Entry Criteria

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


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 fluovoxamine)
    • 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)

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

Expected Enrollment

930

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

Outcomes

Primary Outcome(s)

Survival
Progression-free survival

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.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

David Quinn, MD, Protocol chair
Ph: 323-865-3956
Email: diquinn@hsc.usc.edu
Maha Hadi Hussain, MD, Protocol co-chair
Ph: 734-936-8906; 800-865-1125
Primo Lara, MD, Protocol co-chair
Ph: 916-734-3771
Mark Garzotto, MD, Protocol co-chair
Ph: 503-220-8262 ext. 51982
Email: garzotto@ohsu.edu

Trial Sites

U.S.A.
Alaska
  Anchorage
 Alaska Regional Hospital Cancer Center
 Saul Rivkin, MD
Ph: 206-386-2929
California
  Arroyo Grande
 Arroyo Grande Community Hospital
 David Palchak, MD
Ph: 805-473-8983
  Castro Valley
 East Bay Radiation Oncology Center
 James Feusner, MD
Ph: 510-428-3689
 Eden Medical Center
 James Feusner, MD
Ph: 510-428-3689
 Valley Medical Oncology Consultants - Castro Valley
 James Feusner, MD
Ph: 510-428-3689
  Fremont
 Valley Medical Oncology
 James Feusner, MD
Ph: 510-428-3689
  Loma Linda
 Veterans Affairs Medical Center - Loma Linda (Pettis)
 Mark Reeves, MD, PhD
Ph: 909-825-7084
  Los Angeles
 USC/Norris Comprehensive Cancer Center and Hospital
 Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital
Ph: 323-865-0451
  Marysville
 Tibotec Therapeutics - Division of Ortho Biotech Products, LP
 Primo Lara, Jr.
Ph: 908-541-4500
  Oakland
 Alta Bates Summit Medical Center - Summit Campus
 Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus
Ph: 510-204-1414
 Bay Area Breast Surgeons, Incorporated
 James Feusner, MD
Ph: 510-428-3689
 CCOP - Bay Area Tumor Institute
 James Feusner, MD
Ph: 510-428-3689
 Highland General Hospital
 James Feusner, MD
Ph: 510-428-3689
 Larry G Strieff MD Medical Corporation
 James Feusner, MD
Ph: 510-428-3689
 Tom K Lee, Incorporated
 James Feusner, MD
Ph: 510-428-3689
  Pleasanton
 Valley Care Medical Center
 James Feusner, MD
Ph: 510-428-3689
 Valley Medical Oncology Consultants - Pleasanton
 James Feusner, MD
Ph: 510-428-3689
  Sacramento
 University of California Davis Cancer Center
 Clinical Trials Office - University of California Davis Cancer Center
Ph: 916-734-3089
  San Pablo
 Doctors Medical Center - San Pablo Campus
 James Feusner, MD
Ph: 510-428-3689
Colorado
  Aurora
 Aurora Presbyterian Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
 University of Colorado Cancer Center at UC Health Sciences Center
 Clinical Trials Office - University of Colorado Cancer Center
Ph: 720-848-0650
  Boulder
 Boulder Community Hospital
 Clinical Trials Office - Boulder Community Hospital
Ph: 303-938-5253
  Colorado Springs
 Penrose Cancer Center at Penrose Hospital
 Clinical Trials Office - Penrose Cancer Center
Ph: 719-776-5275
  Denver
 CCOP - Colorado Cancer Research Program
 Eduardo Pajon, MD
Ph: 303-777-2663
 Porter Adventist Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
 Presbyterian - St. Luke's Medical Center
 Clinical Trials Office - Presbyterian - St. Luke's Medical Center
Ph: 303-839-6000
 Rose Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
 St. Anthony Central Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
 St. Joseph Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
 Veterans Affairs Medical Center - Denver
 Anthony Elias, MD
Ph: 303-399-8020
888-336-8262
  Edwards
 Shaw Regional Cancer Center
 Anthony Elias, MD
Ph: 970-569-7429
  Englewood
 Swedish Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Fort Collins
 Front Range Cancer Specialists
 Diana Medgyesy, MD
Ph: 970-212-7600
 Poudre Valley Hospital
 Clinical Trials Office - Poudre Valley Hospital
Ph: 970-495-8226
  Grand Junction
 St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Greeley
 North Colorado Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Lone Tree
 Sky Ridge Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Longmont
 Hope Cancer Care Center at Longmont United Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
  Loveland
 McKee Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Montrose
 Montrose Memorial Hospital Cancer Center
 Clinical Trials Office - Montrose Memorial Hospital Cancer Center
Ph: 670-240-7267
  Pueblo
 St. Mary - Corwin Regional Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Thornton
 North Suburban Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Wheat Ridge
 Exempla Lutheran Medical Center
 Clinical Trials Office - Exempla Lutheran Medical Center
Ph: 303-403-3605
Connecticut
  Manchester
 Manchester Memorial Hospital
 Jeffrey Wasser, MD
Ph: 860-646-0670
District of Columbia
  Washington
 Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
 Clinical Trials Office - Lombardi Comprehensive Cancer Center
Ph: 202-444-0381
 Veterans Affairs Medical Center - Washington, DC
 Anthony Arcenas
Ph: 202-745-8178
888-553-0242
Florida
  Fort Lauderdale
 Broward General Medical Center Cancer Center
 Clinical Trials Office - Broward General Medical Center Cancer Center
Ph: 954-355-5346
  Hollywood
 Memorial Cancer Institute at Memorial Regional Hospital
 Clinical Trials Office - Memorial Cancer Institute
Ph: 954-985-3443
  Orange Park
 Integrated Community Oncology Network - Orange Park
 Linda Struhar-Sylvester, MD, FACP
Ph: 904-272-3139
  Orlando
 Florida Hospital Cancer Institute at Florida Hospital Orlando
 Clinical Trials Office - Florida Hospital Cancer Institute
Ph: 407-303-5623
  Titusville
 Space Coast Medical Associates
 Ashish Dalal
Ph: 321-268-4200
Georgia
  Atlanta
 CCOP - Atlanta Regional
 Thomas Seay, MD, PhD
Ph: 404-851-2340
 Northside Hospital Cancer Center
 Clinical Trials Office - Northside Hospital Cancer Center
Ph: 404-303-3355
 Piedmont Hospital
 Thomas Seay, MD, PhD
Ph: 404-851-2340
 Saint Joseph's Hospital of Atlanta
 Clinical Trials Office - Saint Joseph's Hospital of Atlanta
Ph: 404-851-7115
  Austell
 WellStar Cobb Hospital
 Clinical Trials Office - WellStar Cobb Hospital
Ph: 770-793-5980
  Decatur
 Charles B. Eberhart Cancer Center at DeKalb Medical Center
 Thomas Seay, MD, PhD
Ph: 404-851-2340
  Lawrenceville
 Gwinnett Medical Center
 Thomas Seay, MD, PhD
Ph: 404-851-2340
  Marietta
 Kennestone Cancer Center at Wellstar Kennestone Hospital
 Clinical Trials Office - Kennestone Cancer Center
Ph: 770-793-5980
  Riverdale
 Southern Regional Medical Center
 Clinical Trials Office - Southern Regional Medical Center
Ph: 770-991-8611
Illinois
  Alton
 Saint Anthony's Hospital at Saint Anthony's Health Center
 Bethany Sleckman, MD
Ph: 314-251-6573
  Aurora
 Rush-Copley Cancer Care Center
 Kendrith Rowland, MD
Ph: 217-383-3010
  Chicago
 Resurrection Medical Center
 Christopher Rose, MD
Ph: 773-792-5116
877-737-4636
  Decatur
 Decatur Memorial Hospital Cancer Care Institute
 Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute
Ph: 217-876-6601
  Elmhurst
 Elmhurst Memorial Hospital
 Gerald Kozuh, MD
Ph: 630-833-1400
  Hines
 Veterans Affairs Medical Center - Hines
 Nirmala Bhoopalam, MD
Ph: 708-202-8387 ext. 22782
  Joliet
 Joliet Oncology-Hematology Associates, Limited - West
 Kendrith Rowland, MD
Ph: 217-383-3010
  Maywood
 Cardinal Bernardin Cancer Center at Loyola University Medical Center
 Clinical Trials Office - Cardinal Bernardin Cancer Center
Ph: 708-226-4357
  Mt. Vernon
 Good Samaritan Regional Health Center
 Bethany Sleckman, MD
Ph: 314-251-6573
  Rockford
 Swedish-American Regional Cancer Center
 Clinical Trials Office - Swedish-American Regional Cancer Center
Ph: 815-489-4413
  Springfield
 Regional Cancer Center at Memorial Medical Center
 Clinical Trials Office - Regional Cancer Center at Memorial Medical Center
Ph: 217-788-4233
  Urbana
 Carle Cancer Center at Carle Foundation Hospital
 Clinical Trials Office - Carle Cancer Center
Ph: 800-446-5532
 CCOP - Carle Cancer Center
 Clinical Trials Office - CCOP - Carle Cancer Center
Ph: 800-446-5532
Indiana
  Beech Grove
 St. Francis Hospital and Health Centers - Beech Grove Campus
 Howard Gross, MD
Ph: 317-787-3311
  Bloomington
 Bloomington Hospital Regional Cancer Institute
 David Lee, MD
Ph: 812-353-4673
866-992-4673
  Elkhart
 Elkhart General Hospital
 Robin Zon, MD
Ph: 574-294-2621
  Goshen
 Center for Cancer Care at Goshen General Hospital
 Clinical Trials Office - Center for Cancer Care at Goshen General Hospital
Ph: 574-535-2858
  Indianapolis
 Indiana University Melvin and Bren Simon Cancer Center
 Clinical Trials Office - Indiana University Cancer Center
Ph: 317-274-2552
 Veterans Affairs Medical Center - Indianapolis
 Noah Hahn
Ph: 317-554-0000
888-878-6889
 William N. Wishard Memorial Hospital
 Noah Hahn
Ph: 317-639-6671
  Kokomo
 Howard Community Hospital
 Robin Zon, MD
Ph: 765-453-8571
  La Porte