Back to resultsCombination Chemotherapy in Treating Pain in Hormone Refractory Metastatic Prostate Cancer
Primary Purpose
Pain, Prostate Cancer, Quality of Life
Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
clodronate disodium
mitoxantrone hydrochloride
prednisone
quality-of-life assessment
Sponsored by
About this trial
This is an interventional treatment trial for Pain focused on measuring adenocarcinoma of the prostate, recurrent prostate cancer, pain, quality of life
Eligibility 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
Sites / Locations
- Tom Baker Cancer Center - Calgary
- Penticton Regional Hospital
- British Columbia Cancer Agency - Fraser Valley Cancer Centre
- B.C. Cancer Agency
- Saint John Regional Hospital
- Newfoundland Cancer Treatment and Research Foundation
- Nova Scotia Cancer Centre
- Cancer Care Ontario-Hamilton Regional Cancer Centre
- Kingston Regional Cancer Centre
- Cancer Care Ontario-London Regional Cancer Centre
- Trillium Health Centre
- Ottawa Regional Cancer Center - General Division
- Peterborough Oncology Clinic
- Hotel Dieu Hospital - St. Catharines
- Northwestern Ontario Regional Cancer Centre, Thunder Bay
- Toronto Sunnybrook Regional Cancer Centre
- Princess Margaret Hospital
- Humber River Regional Hospital
- Cancer Care Ontario - Windsor Regional Cancer Centre
- Queen Elizabeth Hospital, PEI
- McGill University Department of Oncology
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00003232
First Posted
November 1, 1999
Last Updated
April 1, 2020
Sponsor
NCIC Clinical Trials Group
1. Study Identification
Unique Protocol Identification Number
NCT00003232
Brief Title
Combination Chemotherapy in Treating Pain in Hormone Refractory Metastatic Prostate Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
November 24, 1997 (Actual)
Primary Completion Date
May 1, 2002 (Actual)
Study Completion Date
February 10, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NCIC Clinical Trials Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Prostate Cancer, Quality of Life
Keywords
adenocarcinoma of the prostate, recurrent prostate cancer, pain, quality of life
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
227 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
clodronate disodium
Intervention Type
Drug
Intervention Name(s)
mitoxantrone hydrochloride
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
10. Eligibility
Sex
Male
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donald S. Ernst, MD, FRCPC
Organizational Affiliation
Tom Baker Cancer Centre - Calgary
Official's Role
Study Chair
Facility Information:
Facility Name
Tom Baker Cancer Center - Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Penticton Regional Hospital
City
Penticton
State/Province
British Columbia
ZIP/Postal Code
V2A 3G6
Country
Canada
Facility Name
British Columbia Cancer Agency - Fraser Valley Cancer Centre
City
Surrey
State/Province
British Columbia
ZIP/Postal Code
V3V 1Z2
Country
Canada
Facility Name
B.C. Cancer Agency
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Saint John Regional Hospital
City
Saint John
State/Province
New Brunswick
ZIP/Postal Code
E2L 4L2
Country
Canada
Facility Name
Newfoundland Cancer Treatment and Research Foundation
City
St. Johns
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
Nova Scotia Cancer Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
Cancer Care Ontario-Hamilton Regional Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Kingston Regional Cancer Centre
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
Cancer Care Ontario-London Regional Cancer Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Trillium Health Centre
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5B 1B8
Country
Canada
Facility Name
Ottawa Regional Cancer Center - General Division
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Peterborough Oncology Clinic
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9H 7B6
Country
Canada
Facility Name
Hotel Dieu Hospital - St. Catharines
City
St. Catharines
State/Province
Ontario
ZIP/Postal Code
L2R 5K3
Country
Canada
Facility Name
Northwestern Ontario Regional Cancer Centre, Thunder Bay
City
Thunder Bay
State/Province
Ontario
ZIP/Postal Code
P7A 7T1
Country
Canada
Facility Name
Toronto Sunnybrook Regional Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Humber River Regional Hospital
City
Weston
State/Province
Ontario
ZIP/Postal Code
M9N 1N8
Country
Canada
Facility Name
Cancer Care Ontario - Windsor Regional Cancer Centre
City
Windsor
State/Province
Ontario
ZIP/Postal Code
N8W 2X3
Country
Canada
Facility Name
Queen Elizabeth Hospital, PEI
City
Charlottetown
State/Province
Prince Edward Island
ZIP/Postal Code
C1A 8T5
Country
Canada
Facility Name
McGill University Department of Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
Citation
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.
Results Reference
result
PubMed Identifier
12947070
Citation
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.
Results Reference
result
PubMed Identifier
33270906
Citation
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.
Results Reference
derived
Learn more about this trial
Combination Chemotherapy in Treating Pain in Hormone Refractory Metastatic Prostate Cancer
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