Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Randomized, Controlled Study of Maximum Androgen Blockade With vs. Without Zoledronic Acid in Prostatic Cancer Patients With Metastatic Bone Disease
Brief Summary: RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen blockade therapy may lessen the amount of androgens made by the body. Zoledronic acid may help relieve some of the symptoms caused by bone metastasis. It is not yet known whether androgen-blockade therapy is more effective with or without zoledronic acid in treating patients with prostate cancer that has spread to the bone.

PURPOSE: This randomized phase III trial is studying androgen-blockade therapy given together with zoledronic acid to see how well it works compared with androgen-blockade therapy alone in treating patients with prostate cancer and bone metastases.


Options:
A: Inclusion Criteria:

* Men \>/= 18 years of age with histologically confirmed prostate cancer
* Radiographic evidence of at least one bone metastasis
* Failure of at least one hormonal therapy as evidenced by a rising PSA
* Serum testosterone level of \<50 ng/dL
* ECOG PS 0, 1, or 2
* Adequate organ function

Exclusion Criteria:

* Current or prior IV bisphosphonate administration
* Current or prior oral bisphosphonates for bone mets
* Life expectancy of less than 6 months
B: PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-- Histologically confirmed adenocarcinoma of the prostate Androgen independent with at least 1 bone lesion that is felt to be associated with metastatic disease Refractory disease must be demonstrated after the withdrawal of flutamide, nilutamide, bicalutamide, or any other antiandrogen Clinically progressive disease for at least 1 month documented by rising PSA levels, at least 1 new metastatic deposit on Tc-99 bone scintigraphy, increasing measurable disease, or new areas of malignant disease Patients with PSA-negative disease (i.e., PSA less than 10 ng/mL) must have positive CT scans of soft tissue disease that can be used for disease staging, bone scan, or some other form of documentable disease progression (i.e., rising carcinoembryonic antigen, prostatic acid phosphatase) Testosterone in the range expected for castrated males No brain metastases or primary CNS malignancies No unresolved acute local complications that require urgent local medical therapy (such as severe bone pain, spinal cord compression, or urinary flow obstruction) --Prior/Concurrent Therapy-- Biologic therapy: Not specified Chemotherapy: No prior ketoconazole for prostate cancer Endocrine therapy: See Disease Characteristics Treatment with LHRH agonist must continue for those patients who have not undergone surgical castration If LHRH agonist has been discontinued, it must be reinstituted with documented disease progression At least 4 weeks since prior hormonal therapy other than LHRH agonist and recovered Radiotherapy: Prior radiotherapy to the prostate allowed At least 4 weeks since prior radiotherapy and recovered Surgery: Prior radical prostatectomy allowed At least 4 weeks since prior surgery and recovered Other: At least 4 weeks since other prior anti-cancer therapy and recovered No prior transfusion with strontium chloride Sr 89 and/or samarium Sm 153 lexidronam pentasodium No concurrent phenytoin, theophylline, cisapride, triazolam, astemizole, loratadine, rifampin, isoniazid, erythromycin, terfenadine, midazolam, alprazolam, atorvastatin calcium, cerivastatin sodium, dofetilide, lovastatin, pimozide, simvastatin, or sirolimus No concurrent drugs that decrease gastric acid output or increase gastric pH (e.g., antacids, cimetidine, ranitidine, or antimuscarinics) No concurrent warfarin --Patient Characteristics-- Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Greater than 3 months Hematopoietic: Granulocyte count at least 1,000/mm3 Hemoglobin at least 8.0 g/dL (pretreatment transfusion allowed, provided hemoglobin is maintained for more than 30 days without additional transfusions and/or an active source of bleeding is identified and treated) Platelet count at least 75,000/mm3 Hepatic: Acute care panel (i.e., electrolytes, BUN) and urinalysis normal Bilirubin no greater than 1.2 mg/dL ALT less than 2.5 times upper limit of normal AST less than 2.5 times normal Renal: Creatinine no greater than 1.5 mg/dL and no proteinuria present OR Creatinine clearance greater than 40 mL/min and proteinuria less than 500 mg/day (proteinuria not an exclusion for patients with stents in place) Cardiovascular: No history of unstable or newly diagnosed angina pectoris No myocardial infarction within the past 6 months No New York Heart Association class II-IV congestive heart failure Pulmonary: No chronic obstructive lung disease requiring oxygen therapy Neurologic: No uncontrolled seizure activity No history of seizures within the past 10 years Other: No other prior malignancies within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the bladder No other life-threatening illnesses No untreated infection HIV negative Willingness to travel from home to NIH for follow-up visits
C: Inclusion Criteria:

* Patients with definitive diagnosis of prostatic cancer by histopathological diagnosis or cytology
* Androgen blockade therapy-, systemic chemotherapy-, bisphosphonates-naïve prostatic cancer patients
* Patients who are sensitive to androgen blockade therapy
* Patients with bone metastasis on bone scan (EOD ≥ 1)
* Patients who have Eastern Cooperative Oncology Group performance status (ECOG: 0-2)
* Patients who have prostate-specific antigen performance status (PSA ≧30 ng/mL)
* Patients who demonstrate appropriate bone marrow, hepatic and renal functions in laboratory tests within four weeks before the registration.

  * Leukocyte count ≥ 3,000/μL
  * Hemoglobin ≥ 9.0 g/dL
  * Platelet count ≥ 7.5 × 10\^4/μL
  * Serum creatine level ≤ 3.0 mg/dL
  * 8.5 mg/dL ≤ corrected serum level of calcium ≤ 11.5 mg/dL
  * Total bilirubin ≤ 1.8 mg/dL
  * Aspartate aminotransferase (AST) Levels ≤ 90 IU/L
  * Alanine aminotransferase (ALT) Levels ≤ 100 IU/L
  * Patients who agreed to participate in this clinical study in writing after receiving sufficient explanation

Exclusion criteria:

* Patients with poorly-controlled dental caries
* Patients with double cancer that requires treatment
* Patients who are using following steroid drugs (except for topical ointment)
* Patients with poorly-controlled hypertension or cardiovascular disease
* Patients with active infectious diseases or HIV or hepatitis virus infections
* Other patients whose participation in the present study is considered inappropriate by a Principal Investigator or Clinical Investigator

PRIOR CONCURRENT THERAPY:

* No prior androgen-blockade therapy
* No prior or other concurrent anticancer therapy
* No prior or concurrent immunologic adjuvant therapy
* No prior or concurrent steroid drugs (except ointment)
* No other prior or concurrent bisphosphonates (excluding zoledronic acid)
* No prior systemic chemotherapy
D: DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate or metastatic carcinoma of presumptive prostate origin as manifest by the presence of sclerotic bony metastases and a serum PSA level greater than the upper limit of normal Radiologically proven progressive bone disease (e.g., new bone scan lesions, increased uptake of isotope at previous sites of disease, and/or increasing bone pain) Hormone refractory disease (i.e., disease progression or recurrence despite documented castrate levels of serum testosterone achieved by bilateral orchiectomy or antiandrogen therapy) Bone pain due to metastatic disease Patients must have achieved stable analgesia for at least 7 days No uncontrolled epidural metastases

PATIENT CHARACTERISTICS: Age: Any age Performance status: ECOG 0-3 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Absolute granulocyte count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin no greater than 3.15 mg/dL Renal: Creatinine less than 2.26 mg/dL Serum calcium no greater than 3.1 mmol/L Cardiovascular: Patients with history of angina pectoris, previous cardiac infarction, hypertension, or valvular or congenital heart disease must have baseline measurement of LVEF exceeding 50% Other: No other malignancy within 5 years except nonmelanomatous skin cancer No active infection or any other contraindication to chemotherapy with mitoxantrone No spinal cord or nerve root compression No unstabilized impending pathological fractures

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: One previous course of chemotherapy allowed No prior mitoxantrone or other anthracycline Endocrine therapy: See Disease Characteristics At least 4 weeks since prior nonsteroidal antiandrogens Radiotherapy: At least 4 weeks since prior radiotherapy At least 8 weeks since prior strontium-89 or samarium-153 Surgery: Not specified Other: No prior bisphosphonate therapy

Answer: C