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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00329797
First received: May 23, 2006
Last updated: January 10, 2014
Last verified: January 2014
  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 acetate
Drug: leuprolide acetate
Drug: triptorelin
Drug: zoledronic acid
Radiation: brachytherapy
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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 Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Freedom from any bone fracture [ Time Frame: From randomization to date of documented bone fracture(s) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent change in bone mineral density at 3 years [ Time Frame: From pre-treatment to 3 years from start of treatment ] [ Designated as safety issue: No ]
  • Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General [ Time Frame: From pre-treatment to 3 years from start of treatment ] [ Designated as safety issue: No ]
  • Utility of the use of bisphosphonates as assessed by the European Questionnaire-5 Dimensional [ Time Frame: From pre-treatment to 3 years from start of treatment ] [ Designated as safety issue: No ]

Enrollment: 109
Study Start Date: March 2006
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Parents receive zoledronate IV over 15 minutes once every 6 months. Patients also receive oral calcium and oral cholecalciferol (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., leuprolide 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 acetate
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
Active Comparator: 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. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuprolide 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 acetate
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 cholecalciferol (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., leuprolide 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 Characteristics
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 88 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Colleen A. Lawton, MD Medical College of Wisconsin
Study Chair: Matthew R. Smith, MD Massachusetts General Hospital
Study Chair: Margaret Chamberlain-Wilmoth, PhD, MSS, RN Carolinas Medical Center - University
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00329797     History of Changes
Other Study ID Numbers: RTOG 0518, CDR0000476469, NCI-2009-00884
Study First Received: May 23, 2006
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
osteoporosis
adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Osteoporosis
Prostatic Neoplasms
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Buserelin
Leuprolide
Triptorelin
Zoledronic acid
Calcium, Dietary
Cholecalciferol
Calcium Carbonate
Goserelin
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Bone Density Conservation Agents
Antacids
Molecular Mechanisms of Pharmacological Action
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on July 24, 2014