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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
1,038
Given orally
Docetaxel given IV and prednisone given orally
Docetaxel given IV and prednisone given orally
Given orally
Providence Cancer Center at Providence Hospital
Mobile, Alabama, United States
Alaska Regional Hospital Cancer Center
Anchorage, Alaska, United States
Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States
Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.
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
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.
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
Compare Pain Progression Between the Two Study Arms.
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
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms
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
Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm.
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
Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria.
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
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Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
Fort Smith, Arkansas, United States
East Bay Radiation Oncology Center
Castro Valley, California, United States
Eden Medical Center
Castro Valley, California, United States
Valley Medical Oncology Consultants - Castro Valley
Castro Valley, California, United States
Valley Medical Oncology
Fremont, California, United States
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