Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Placebo-Controlled Trial of Mitoxantrone/Prednisone and Clodronate Versus Mitoxantrone/Prednisone Alone in Patients With Hormone Refractory Metastatic Prostate Cancer and Pain
Brief Summary: RATIONALE: Some drugs used in chemotherapy can reduce the pain experienced by some people with cancer. Combining more than one drug may be more effective at reducing cancer pain. It is not known whether receiving combination chemotherapy with clodronate is more effective than receiving combination chemotherapy without clodronate for hormone refractory metastatic prostate cancer.

PURPOSE: Randomized double-blinded phase III trial to compare the effectiveness of combination chemotherapy using mitoxantrone plus prednisone with or without clodronate in treating pain in patients with hormone refractory metastatic prostate cancer.


Options:
A: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate with metastatic bone disease (by CT, MRI or bone scan) with plans to start or be \< 30 days from beginning androgen deprivation therapy. Patients with lymph node or visceral metastases only are not eligible
* Patients may receive palliative radiation therapy at the investigators discretion during the first 4 weeks of beginning protocol therapy.

Exclusion Criteria:

* No neuroendocrine, small cell or transitional cell cancer of the prostate No abnormal bone metabolism (i.e., Paget's disease, untreated hyperthyroidism, untreated hyperprolactinemia, untreated Cushing's disease).
* No use of calcitonin within 14 days before being registered for protocol therapy or any previous use of bisphosphonates.
* No major surgery within 4 weeks of registration to protocol therapy.
* No adjuvant chemotherapy within 6 months of registration to protocol therapy.
* No previous chemotherapy for metastatic disease.
* No hormonal therapy in the adjuvant setting within 12 months of registration to protocol therapy; previous hormonal therapy must not have exceeded 6 months.
* No prior history of malignancy in the past 5 years with the exception of basal cell and squamous cell carcinoma of the skin.
* No history of allergy or drug reactions to bisphosphonates.
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: D