Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients With Prostate Cancer

Osteoporosis Prevention in Prostate Cancer Patients Receiving Androgen Ablation Therapy: A Phase III Randomized, Placebo-Controlled, Double-Blind Study

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Osteoporosis
• Intervention / Treatment: Other: placebo; Dietary supplement: cholecalciferol; Drug: risedronate sodium; Dietary supplement: calcium carbonate; Drug: Estrogen Antagonists

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
    • Regina, Saskatchewan, Canada, S4T 1A5
      • Pasqua Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • CCOP - Mayo Clinic Scottsdale Oncology Program
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic - Jacksonville
  • Illinois
    • Aurora, Illinois, United States, 60507
      • Rush-Copley Cancer Care Center
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic
    • Galesburg, Illinois, United States, 61401
      • InterCommunity Cancer Center of Western Illinois
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology Hematology Associates, Limited - West
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology/Hematology Associates of Central Illinois, P.C.
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • St. Margaret's Hospital
    • Spring Valley, Illinois, United States, 61362
      • Valley Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, P.C.
    • Carroll, Iowa, United States, 51401
      • Saint Anthony Regional Hospital
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol Hospital
    • Mason City, Iowa, United States, 50401
      • Mercy Cancer Center at Mercy Medical Center - North Iowa
    • Missouri Valley, Iowa, United States, 51555
      • Alegent Health Community Memorial Hospital
    • Onawa, Iowa, United States, 51040
      • Burgess Health Center
    • Ottumwa, Iowa, United States, 52501
      • Cancer Center at Ottumwa Regional Health Center
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates
    • West Des Moines, Iowa, United States, 50266
      • Medical Oncology and Hematology Associates - West Des Moines
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, P.A. - El Dorado
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, P.A. - Parsons
    • Pratt, Kansas, United States, 67124
      • Pratt Cancer Center of Kansas
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67203
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, P.A.
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, P.A. - Wichita
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Minnesota
    • Brainerd, Minnesota, United States, 56401
      • Brainerd Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805
      • St. Mary's - Duluth Clinic Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Medical Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Mercy and Unity Hospitals
    • Minneapolis, Minnesota, United States, 55403
      • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422
      • Hubert H. Humphrey Cancer Center at North Memorial Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • St. Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
    • St. Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic
    • St. Paul, Minnesota, United States, 55102
      • United Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Sletten Regional Cancer Institute
  • Nebraska
    • Fremont, Nebraska, United States, 68025
      • Fremont Area Medical Center
    • Lincoln, Nebraska, United States, 68502
      • Bryan LGH Medical Center West
    • Lincoln, Nebraska, United States, 68510
      • Cancer Resource Center - Lincoln
    • Lincoln, Nebraska, United States, 68510
      • St. Elizabeth Regional Medical Center
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131
      • Cancer Center at Creighton University Medical Center
    • Papillion, Nebraska, United States, 68046
      • Midlands Cancer Center at Midlands Community Hospital
  • North Carolina
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Health System
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, P.C.
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • St. Alexius Medical Center
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center at Altru Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • Geisinger Medical Center
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Rose Ramer Cancer Clinic at Anderson Area Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
    • Spartanburg, South Carolina, United States, 29304
      • CCOP - Upstate Carolina
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center
    • Sioux Falls, South Dakota, United States, 57104
      • Sioux Valley Hospital and University of South Dakota Medical Center
    • Sioux Falls, South Dakota, United States, 57105
      • Avera McKennan Hospital and University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm I: calcium + cholecalciferol + placebo + estrogen; Patients receive oral calcium, oral cholecalciferol, oral risedronate placebo, and oral estrogen placebo 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.	Other: placebo; Dietary supplement: cholecalciferol; Dietary supplement: calcium carbonate; Drug: Estrogen Antagonists
EXPERIMENTAL: Arm II: calcium + cholecalciferol + risedronate + estrogen; Patients receive oral calcium, oral cholecalciferol, oral risedronate, and oral estrogen placebo 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.	Dietary supplement: cholecalciferol; Drug: risedronate sodium; Dietary supplement: calcium carbonate; Drug: Estrogen Antagonists
PLACEBO_COMPARATOR: Arm III: calcium + cholecalciferol + placebo + estrogen; Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate placebo 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.	Other: placebo; Dietary supplement: cholecalciferol; Dietary supplement: calcium carbonate; Drug: Estrogen Antagonists
EXPERIMENTAL: Arm IV: calcium + cholecalciferol + risedronate + estrogen; 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.	Dietary supplement: cholecalciferol; Drug: risedronate sodium; Dietary supplement: calcium carbonate; Drug: Estrogen Antagonists

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bone mineral density by test at 1 and 2 years	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity questionnaires every 6 months	6 months

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Primary Completion (ACTUAL): June 1, 2006
• Study Completion (ACTUAL): January 1, 2010

Study Registration Dates

• First Submitted: August 5, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: stage III prostate cancer; osteoporosis; stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Metabolic Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Prostatic Neoplasms; Osteoporosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Membrane Transport Modulators; Hormone Antagonists; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antacids; Cholecalciferol; Risedronic Acid; Calcium Carbonate; Estrogens; Estrogen Antagonists; Estrogen Receptor Antagonists
• Other Study ID Numbers: NCCTG-N01C8; NCI-2012-02482 (REGISTRY: CTRP (Clinical Trials Reporting System)); NCI-P02-0229; CDR0000069502 (REGISTRY: PDQ (Physician Data Query))