Combination Chemotherapy in Treating Pain in Hormone Refractory Metastatic Prostate Cancer

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003232

Collaborator

(none)

227

Enrollment

Locations

134.6

Actual Duration (Months)

10.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

227 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

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

Actual Study Start Date :

Nov 24, 1997

Actual Primary Completion Date :

May 1, 2002

Actual Study Completion Date :

Feb 10, 2009

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 120 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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