Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer

Inclusion 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

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 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)