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

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

Outcomes

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

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