Clinical trial NCT00043069: Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients With Prostate Cancer
Official title: Osteoporosis Prevention in Prostate Cancer Patients Receiving Androgen Ablation Therapy: A Phase III Randomized, Placebo-Controlled, Double-Blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Prostate Cancer
Keywords: osteoporosis
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 71
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Preventing bone loss in patients who are undergoing androgen ablation for prostate cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without estrogen and/or risedronate in preventing osteoporosis.

PURPOSE: Randomized phase III trial to compare the effectiveness of two forms of calcium with or without estrogen and/or risedronate in preventing osteoporosis in patients with prostate cancer who are receiving androgen ablation therapy.

Detailed description: OBJECTIVES:

* Compare the change in bone mineral density in patients with prostate cancer who are receiving androgen-ablation therapy treated with calcium and cholecalciferol with or without conjugated estrogens and with or without risedronate.
* Compare the toxicity of these regimens in these patients.
* Compare the changes in bone markers in patients treated with these regimens.
* Compare the quality of life of patients treated with these regimens.
* Compare hot flashes in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to duration of therapy with luteinizing hormone-releasing hormone agonists (no more than 30 days vs 31 to 150 days vs 151 to 365 days vs more than 365 days). Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive oral calcium, oral cholecalciferol, oral risedronate placebo, and oral estrogen placebo daily.
* Arm II: Patients receive oral calcium, oral cholecalciferol, oral risedronate, and oral estrogen placebo daily.
* Arm III: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate placebo daily.
* Arm IV: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate daily.

Treatment in all arms continues for 2 years.

Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years.

Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years.

PROJECTED ACCRUAL: A total of 282 patients (70 per treatment arm) will be accrued for this study within 14 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* History of prostate cancer

  * No evidence of metastatic bony disease\* NOTE: \*Elevated prostate-specific antigen (PSA) allowed
* Meets one of the following criteria:

  * Currently on treatment with androgen-ablation therapy in the adjuvant setting
  * Rising PSA without other evidence of recurrent disease with planned treatment for at least 6 months
* No known osteoporosis or prior osteoporotic fracture

  * Osteoporosis defined as bone density at the hip or spine of more than 2.5 standard deviations below the mean for young men

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* SGOT or SGPT no greater than 1.5 times upper limit of normal (ULN)
* Alkaline phosphatase normal OR no greater than 1.5 times ULN with a normal bone scan

Renal

* Creatinine no greater than 1.5 times ULN
* No prior symptomatic hypercalcemia or hypocalcemia

Cardiovascular

* No active heart disease
* No congestive heart failure under active treatment
* No myocardial infarction within the past 5 years
* No coronary artery disease (CAD) with recent myocardial infarction

  * Patients with a remote history of CAD who are only on medical treatment (e.g., antilipid agents) are allowed
* No prior thrombosis (deep vein thrombosis, stroke, or pulmonary embolism) or other known hypercoagulable state other than cancer

Other

* Fertile patients must use effective contraception
* Triglycerides no greater than 250 mg/dL (treatment allowed)
* Able to complete questionnaire(s) by self or with assistance
* Able to swallow pills
* No prior hyperlipidemia (e.g., prior familial hyperlipidemia or fasting triglyceride greater than 250 mg/dL within the past 6 months)
* No sarcoidosis
* No parathyroid dysfunction
* No intolerance to bisphosphonates

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No concurrent chemotherapy

Endocrine therapy

* See Disease Characteristics
* No concurrent systemic steroids

Radiotherapy

* No concurrent radiotherapy

Surgery

* More than 3 months since prior and no concurrent dental extraction, root canal, or dental implantation

Other

* No prior bisphosphonates
* More than 5 years since prior percutaneous transluminal coronary angioplasty

Primary outcomes:
measure: Bone mineral density by test at 1 and 2 years
timeFrame: Up to 2 years
Secondary outcomes:
measure: Toxicity questionnaires every 6 months
timeFrame: 6 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Mayo Clinic Scottsdale Oncology Program
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: InterCommunity Cancer Center of Western Illinois
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology Hematology Associates, Limited - West
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Valley Cancer Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, P.C.
state: Iowa
city: Carroll
country: United States
facility: Saint Anthony Regional Hospital
state: Iowa
city: Council Bluffs
country: United States
facility: Alegent Health Mercy Hospital
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Mason City
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - North Iowa
state: Iowa
city: Missouri Valley
country: United States
facility: Alegent Health Community Memorial Hospital
state: Iowa
city: Onawa
country: United States
facility: Burgess Health Center
state: Iowa
city: Ottumwa
country: United States
facility: Cancer Center at Ottumwa Regional Health Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: West Des Moines
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, P.A. - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, P.A. - Parsons
state: Kansas
city: Pratt
country: United States
facility: Pratt Cancer Center of Kansas
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, P.A.
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, P.A. - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Brainerd
country: United States
facility: Brainerd Medical Center
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Medical Center
state: Minnesota
city: Duluth
country: United States
facility: St. Mary's - Duluth Clinic Cancer Center
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Mercy and Unity Hospitals
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: St. Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Clinic
state: Minnesota
city: St. Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Great Falls
country: United States
facility: Sletten Regional Cancer Institute
state: Montana
city: Fremont
country: United States
facility: Fremont Area Medical Center
state: Nebraska
city: Lincoln
country: United States
facility: Bryan LGH Medical Center West
state: Nebraska
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Lincoln
country: United States
facility: St. Elizabeth Regional Medical Center
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Cancer Center at Creighton University Medical Center
state: Nebraska
city: Papillion
country: United States
facility: Midlands Cancer Center at Midlands Community Hospital
state: Nebraska
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Medcenter One Health System
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, P.C.
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center at Altru Hospital
state: North Dakota
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Anderson
country: United States
facility: Rose Ramer Cancer Clinic at Anderson Area Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera McKennan Hospital and University Health Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center
state: South Dakota
city: Regina
country: Canada
facility: Pasqua Hospital
state: Saskatchewan
city: Regina
country: Canada
facility: Allan Blair Cancer Centre at Pasqua Hospital
state: Saskatchewan
Study officials:
affiliation: Mayo Clinic
name: Charles L. Loprinzi, MD
role: STUDY_CHAIR
References:
citation: Kearns AE, Northfelt DW, Dueck AC, Atherton PJ, Dakhil SR, Rowland KM Jr, Fuloria J, Flynn PJ, Dentchev T, Loprinzi CL. Osteoporosis prevention in prostate cancer patients receiving androgen ablation therapy: placebo-controlled double-blind study of estradiol and risedronate: N01C8. Support Care Cancer. 2010 Mar;18(3):321-8. doi: 10.1007/s00520-009-0655-x. Epub 2009 May 27.