Combination Chemotherapy in Treating Pain in Hormone Refractory Metastatic Prostate Cancer

NCT ID: NCT00003232

Last Updated: 2020-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 227 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-11-24
• Study Completion Date: 2009-02-10

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.

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.

Conditions

Pain; Prostate Cancer; Quality of Life

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Interventions

clodronate disodium

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

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

• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald S. Ernst, MD, FRCPC

Role: STUDY_CHAIR

Tom Baker Cancer Centre - Calgary

Locations

Tom Baker Cancer Center - Calgary

Calgary, Alberta, Canada

Penticton Regional Hospital

Penticton, British Columbia, Canada

British Columbia Cancer Agency - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

B.C. Cancer Agency

Vancouver, British Columbia, Canada

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Newfoundland Cancer Treatment and Research Foundation

St. John's, Newfoundland and Labrador, Canada

Nova Scotia Cancer Centre

Halifax, Nova Scotia, Canada

Cancer Care Ontario-Hamilton Regional Cancer Centre

Hamilton, Ontario, Canada

Kingston Regional Cancer Centre

Kingston, Ontario, Canada

Cancer Care Ontario-London Regional Cancer Centre

London, Ontario, Canada

Trillium Health Centre

Mississauga, Ontario, Canada

Ottawa Regional Cancer Center - General Division

Ottawa, Ontario, Canada

Peterborough Oncology Clinic

Peterborough, Ontario, Canada

Hotel Dieu Hospital - St. Catharines

St. Catharines, Ontario, Canada

Northwestern Ontario Regional Cancer Centre, Thunder Bay

Thunder Bay, Ontario, Canada

Toronto Sunnybrook Regional Cancer Centre

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Humber River Regional Hospital

Weston, Ontario, Canada

Cancer Care Ontario - Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Queen Elizabeth Hospital, PEI

Charlottetown, Prince Edward Island, Canada

McGill University Department of Oncology

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: RESULT

Ernst DS, Tannock IF, Winquist EW, Venner PM, Reyno L, Moore MJ, Chi K, Ding K, Elliott C, Parulekar W. Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain. J Clin Oncol. 2003 Sep 1;21(17):3335-42. doi: 10.1200/JCO.2003.03.042.

Reference Type: RESULT

PMID: 12947070 (View on PubMed)

Ernst DS, Tannock IF, Venner PM, et al.: Randomized placebo controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone alone in patients with hormone refractory prostate cancer (HRPC) and pain: National Cancer Insititute of Canada Clinical Trials Group study. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-705, 2002.

Reference Type: RESULT

Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, Heidenreich A, Skoetz N. Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis. Cochrane Database Syst Rev. 2020 Dec 3;12(12):CD013020. doi: 10.1002/14651858.CD013020.pub2.

Reference Type: DERIVED

PMID: 33270906 (View on PubMed)

Other Identifiers

CAN-NCIC-PR6

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000066102

Identifier Type: OTHER

Identifier Source: secondary_id

PR6

Identifier Type: -

Identifier Source: org_study_id