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.

Condition	Treatment or Intervention	Phase
Pain adenocarcinoma of the prostate recurrent prostate cancer Quality of Life	Drug: clodronate  Drug: mitoxantrone  Drug: prednisone	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the effect of mitoxantrone and prednisone with or without clodronate on localized bone pain in patients with hormone refractory metastatic prostate cancer. II. Compare the overall survival and quality of life of these patients after these treatments.

PROTOCOL OUTLINE: This is a randomized, double blinded, placebo controlled, multicenter study. Patients are stratified according to quality of pain (mild vs moderate) and previous corticosteroids or one regimen of non-anthracycline-containing cytotoxic chemotherapy (e.g., estramustine) vs none. Patients are assigned to 1 of 2 treatment arms. Arm I consists of oral prednisone twice a day and intravenous mitoxantrone followed by intravenous clodronate administered over 3 hours every 3 weeks. Arm II consists of oral prednisone twice a day and intravenous mitoxantrone followed by intravenous placebo administered over 3 hours every 3 weeks. Doses are adjusted for myelosuppression. Treatment continues until disease progression (although patients initially on placebo can continue on open-label clodronate) or until the maximum cumulative dose of mitoxantrone is reached. Patients with a palliative response may continue on prednisone and the study drug (clodronate or placebo) until disease progression. Quality of life is assessed before and every 3 weeks during study treatment. A daily pain diary is also maintained. All patients are followed at 2 weeks and then every 3 months until death.

PROJECTED ACCRUAL: This study will accrue 204 patients.

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--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

Canada, Alberta
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, British Columbia
      B.C. Cancer Agency, Vancouver,  British Columbia,  V5Z 4E6,  Canada
      British Columbia Cancer Agency - Fraser Valley Cancer Centre, Surrey,  British Columbia,  V3V 1Z2,  Canada
      Penticton Regional Hospital, Penticton,  British Columbia,  V2A 3G6,  Canada
Canada, New Brunswick
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada
Canada, Ontario
      Cancer Care Ontario - Windsor Regional Cancer Centre, Windsor,  Ontario,  N8W 2X3,  Canada
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Hotel Dieu Hospital - St. Catharines, St. Catharines,  Ontario,  L2R 5K3,  Canada
      Humber River Regional Hospital, Weston,  Ontario,  M9N 1N8,  Canada
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada
      Northwestern Ontario Regional Cancer Centre, Thunder Bay, Thunder Bay,  Ontario,  P7A 7T1,  Canada
      Ottawa Regional Cancer Center - General Division, Ottawa,  Ontario,  K1H 8L6,  Canada
      Peterborough Oncology Clinic, Peterborough,  Ontario,  K9H 7B6,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
      Trillium Health Centre, Mississauga,  Ontario,  L5B 1B8,  Canada
Canada, Prince Edward Island
      Queen Elizabeth Hospital, PEI, Charlottetown,  Prince Edward Island,  C1A 8T5,  Canada
Canada, Quebec
      McGill University Department of Oncology, Montreal,  Quebec,  H2W 1S6,  Canada

Study chairs or principal investigators

D. Scott Ernst,  Study Chair,  National Cancer Institute of Canada   

Study ID Numbers:  CDR0000066102; CAN-NCIC-PR6
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003232
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08