Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00329797

Purpose

RATIONALE: Zoledronate may prevent bone loss in patients with prostate cancer undergoing radiation therapy and hormone therapy. It is not yet known whether zoledronate is more effective than calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with locally advanced nonmetastatic prostate cancer undergoing radiation therapy and hormone therapy.

Condition	Intervention	Phase
Osteoporosis Prostate Cancer	Dietary Supplement: calcium carbonate Dietary Supplement: calcium citrate Dietary Supplement: calcium glucarate Dietary Supplement: cholecalciferol Drug: buserelin Drug: calcium gluconate Drug: goserelin Drug: leuprolide acetate Drug: triptorelin Drug: zoledronic acid Radiation: brachytherapy Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Supportive Care, Randomized
Official Title:	A Phase III Randomized Study to Evaluate the Efficacy of Zometa® for the Prevention of Osteoporosis and Associated Fractures in Patients Receiving Radiation Therapy and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Freedom from any bone fracture [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent change in bone mineral density at 3 years [ Designated as safety issue: No ]
Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General [ Designated as safety issue: No ]
Utility of the use of bisphosphonates as assessed by the European Questionnaire-5 Dimensional [ Designated as safety issue: No ]

Estimated Enrollment:	1272
Study Start Date:	March 2006
Estimated Primary Completion Date:	December 2020 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Parents receive zoledronate IV over 15 minutes once every 6 months. Patients also receive oral calcium and oral cholecaliciferol (vitamin D) once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.	Dietary Supplement: calcium carbonate Given orally Dietary Supplement: calcium citrate Given orally Dietary Supplement: calcium glucarate Given orally Dietary Supplement: cholecalciferol Given orally Drug: buserelin Given concurrently Drug: calcium gluconate Given orally Drug: goserelin Given concurrently Drug: leuprolide acetate Given concurrently Drug: triptorelin Given concurrently Drug: zoledronic acid Given IV Radiation: brachytherapy Given concurrently Radiation: radiation therapy Given concurrently
Arm II: Active Comparator Patients receive oral calcium and oral vitamin D once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.	Dietary Supplement: calcium carbonate Given orally Dietary Supplement: calcium citrate Given orally Dietary Supplement: calcium glucarate Given orally Dietary Supplement: cholecalciferol Given orally Drug: buserelin Given concurrently Drug: calcium gluconate Given orally Drug: goserelin Given concurrently Drug: leuprolide acetate Given concurrently Drug: triptorelin Given concurrently Radiation: brachytherapy Given concurrently Radiation: radiation therapy Given concurrently

Arms

Assigned Interventions

Arm I: Experimental

Parents receive zoledronate IV over 15 minutes once every 6 months. Patients also receive oral calcium and oral cholecaliciferol (vitamin D) once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.

Dietary Supplement: calcium carbonate

Given orally

Dietary Supplement: calcium citrate

Given orally

Dietary Supplement: calcium glucarate

Given orally

Dietary Supplement: cholecalciferol

Given orally

Drug: buserelin

Given concurrently

Drug: calcium gluconate

Given orally

Drug: goserelin

Given concurrently

Drug: leuprolide acetate

Given concurrently

Drug: triptorelin

Given concurrently

Drug: zoledronic acid

Given IV

Radiation: brachytherapy

Given concurrently

Radiation: radiation therapy

Given concurrently

Arm II: Active Comparator

Patients receive oral calcium and oral vitamin D once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.

Dietary Supplement: calcium carbonate

Given orally

Dietary Supplement: calcium citrate

Given orally

Dietary Supplement: calcium glucarate

Given orally

Dietary Supplement: cholecalciferol

Given orally

Drug: buserelin

Given concurrently

Drug: calcium gluconate

Given orally

Drug: goserelin

Given concurrently

Drug: leuprolide acetate

Given concurrently

Drug: triptorelin

Given concurrently

Radiation: brachytherapy

Given concurrently

Radiation: radiation therapy

Given concurrently

Detailed Description:

OBJECTIVES:

Primary

Compare the potential benefit of bisphosphonate therapy comprising zoledronate plus vitamin D and calcium supplement vs standard therapy with vitamin D and calcium supplement in the prevention of osteoporosis and associated bone fractures in patients with locally advanced nonmetastatic adenocarcinoma of the prostate undergoing radiotherapy and luteinizing hormone-releasing hormone (LHRH) agonist therapy.

Secondary

Evaluate the potential benefit of these regimens on quality of life in these patients.
Evaluate the potential benefit in bone mineral density over a period of 3 years for patients treated with these regimens.

OUTLINE: This is randomized multicenter study. Patients are stratified according to T score of the hip by dual x-ray absorptiometry (DXA) scan (< -1.0 but > -2.5 vs ≥ - 1.0) and planned duration of luteinizing hormone-releasing hormone (LHRH) agonist therapy (1-2½ years vs > 2½ years). Patients are randomized to 1 of 2 treatment arms.

Arm I: Parents receive zoledronate IV over 15 minutes once every 6 months. Patients also receive oral calcium and oral cholecaliciferol (vitamin D) once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity.
Arm II: Patients receive oral calcium and oral vitamin D once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity.

All patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.

Quality of life is assessed at baseline and every 6 months during treatment.

PROJECTED ACCRUAL: A total of 1,272 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed adenocarcinoma of the prostate
- Diagnosed within the past 12 months
Any 1 of the following clinical stages:
- Clinical stage T3, any N, M0 with any Gleason score and any prostate-specific antigen (PSA)
- Any T, any N, M0 with one of the following:
  - Gleason score ≥ 8 and any PSA
  - Gleason score 7 and PSA ≥ 15 ng/mL
  - Gleason score < 7 and PSA ≥ 20 ng/mL
Baseline T score > -2.5 in both the L spine and the total hip by dual x-ray absorptiometry (DXA) scan
Planning to receive luteinizing hormone-releasing hormone (LHRH) agonist therapy
- If patient is receiving LHRH therapy before study entry, therapy must have begun ≤ 6 months prior to study entry
- Scheduled to receive a LHRH agonist for ≥ 1 year
Planning to undergo radiotherapy (i.e., external-beam, brachytherapy, or both)
No distant metastases
- Must have negative bone scan for metastatic disease

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
Creatinine clearance > 30 mL/min
Calcium 8.4-10.6 mg/dL
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
No history of Paget's disease
No uncontrolled thyroid or parathyroid dysfunction
No known hypersensitivity to zoledronate or other bisphosphonates
No infection of the teeth or jawbone
No dental or fixture trauma
No current or prior diagnosis of osteonecrosis of the jaw
No exposed bone in the mouth
No slow healing after dental procedures
No other active dental problems
No other diseases that influence bone metabolism
No other malignancy within the past 3 years except nonmelanomatous skin cancer or carcinoma in situ of the breast or oral cavity

PRIOR CONCURRENT THERAPY:

See Disease Characterisitics
More than 6 weeks since prior dental or jaw surgery (e.g., extraction, implants)
No prior bisphosphonate therapy
No prior pelvic radiation
No prior systemic radiotherapeutic agents, such as strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
No concurrent systemic chemotherapy
No concurrent steroids
No concurrent growth hormones
No concurrent calcitonin
No concurrent dental or jaw surgery

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00329797

Show 88 Study Locations

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Colleen A. Lawton, MD	Medical College of Wisconsin
Investigator:	Matthew R. Smith, MD	Massachusetts General Hospital
Investigator:	Margaret Chamberlain-Wilmoth, PhD, MSS, RN	Carolinas Medical Center - University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Radiation Therapy Oncology Group ( Walter John Curran, Jr )
Study ID Numbers:	CDR0000476469, RTOG-0518
Study First Received:	May 23, 2006
Last Updated:	May 27, 2009
ClinicalTrials.gov Identifier:	NCT00329797 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

osteoporosis
adenocarcinoma of the prostate
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:

Buserelin
Molecular Mechanisms of Pharmacological Action
Prostatic Diseases
Genital Neoplasms, Male
Antineoplastic Agents
Contraceptive Agents
Physiological Effects of Drugs
Contraceptive Agents, Female
Bone Density Conservation Agents
Urogenital Neoplasms
Calcium Carbonate
Reproductive Control Agents
Bone Diseases
Neoplasms by Site
Musculoskeletal Diseases

Leuprolide
Vitamins
Therapeutic Uses
Micronutrients
Cholecalciferol
Zoledronic acid
Antineoplastic Agents, Hormonal
Growth Substances
Goserelin
Osteoporosis
Bone Diseases, Metabolic
Luteolytic Agents
Genital Diseases, Male
Pharmacologic Actions
Calcium, Dietary

ClinicalTrials.gov processed this record on February 08, 2010