S0421, 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
Condition: Metastatic Cancer; Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: atrasentan hydrochloride; docetaxel; prednisone; placebo
Intervention description: Given orally; Docetaxel given IV and prednisone given orally; Docetaxel given IV and prednisone given orally; Given orally
Intervention MeSH terms: Prednisone; Docetaxel; Atrasentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1038.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer; bone metastases

Summary:

      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.
    

Eligibility 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 fluvoxamine)

               -  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)