Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer
Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer
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
Secondary
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.
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.
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the prostate
Stage IV disease (any T, any N, M1b)
Measurable or nonmeasurable 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
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
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
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
No more than 1 prior systemic vaccine or biologic therapy
No concurrent biological response modifiers
No concurrent prophylactic colony-stimulating factors
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
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 concurrent herbal medications or food supplements (e.g., PC-SPES, saw palmetto, Hypericum perforatum [St. John's wort])
At least 14 days since prior and no concurrent administration of any of the following:
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