Combination Chemotherapy in Treating Pain in Patients With Hormone Refractory Metastatic Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00003232
Recruitment Status : Completed
First Posted : April 9, 2004
Last Update Posted : November 9, 2010
Information provided by:
Canadian Cancer Trials Group

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.

Condition or disease Intervention/treatment Phase
Pain Prostate Cancer Quality of Life Drug: clodronate disodium Drug: mitoxantrone hydrochloride Drug: prednisone Procedure: quality-of-life assessment Phase 3

Detailed Description:

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.

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 204 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: Randomized Placebo-Controlled Trial of Mitoxantrone/Prednisone and Clodronate Versus Mitoxantrone/Prednisone Alone in Patients With Hormone Refractory Metastatic Prostate Cancer and Pain
Study Start Date : November 1997
Actual Primary Completion Date : February 2009
Actual Study Completion Date : February 2009

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Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00003232

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

Publications of Results:
Taylor SK, Ding K, Ernst SD, et al.: Palliative response measurement in a phase III study of patients with prostate cancer and painful bone metastases: secondary analysis of NCIC-CTG PR6. [Abstract] J Clin Oncol 26 (Suppl 15): A-9636, 2008. Identifier: NCT00003232     History of Changes
Other Study ID Numbers: PR6
CDR0000066102 ( Other Identifier: PDQ )
First Posted: April 9, 2004    Key Record Dates
Last Update Posted: November 9, 2010
Last Verified: November 2010

Keywords provided by Canadian Cancer Trials Group:
adenocarcinoma of the prostate
recurrent prostate cancer
quality of life

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Clodronic Acid
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents