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Zoledronate in Preventing Skeletal (Bone)-Related Events in Patients Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Southwest Oncology Group
Eastern Cooperative Oncology Group
National Cancer Institute of Canada
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079001
  Purpose

RATIONALE: Zoledronate may prevent or decrease skeletal (bone)-related events (such as pain or fractures) caused by bone metastases and androgen deprivation therapy. It is not yet known whether treatment with zoledronate is effective in preventing bone-related events in patients who have prostate cancer and bone metastases.

PURPOSE: This randomized phase III trial is studying how well zoledronate works in preventing bone-related events in patients who are receiving androgen deprivation therapy for prostate cancer and bone metastases.


Condition Intervention Phase
Metastatic Cancer
Prostate Cancer
Drug: placebo
Drug: zoledronic acid
Phase III

MedlinePlus related topics: Cancer Prostate Cancer
Drug Information available for: Zoledronic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Placebo Control
Official Title: A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early Versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men With Prostate Cancer Metastatic to Bone

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

Primary Outcome Measures:
  • Time to first skeletal related event [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 680
Study Start Date: January 2004
Estimated Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental
Patients receive zoledronate IV over 15 minutes on day 1. Courses repeat every 4 weeks in the absence of disease progression or a skeletal-related event.
Drug: zoledronic acid
Given IV
Arm II: Placebo Comparator
Patients receive placebo IV over 15 minutes on day 1. Courses repeat every 4 weeks in the absence of disease progression or a skeletal-related event.
Drug: placebo
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • Compare the time to first skeletal-related events in patients with prostate cancer and bone metastases undergoing androgen deprivation therapy when treated with zoledronate vs placebo.

Secondary

  • Compare the overall and progression-free survival of patients treated with these regimens.
  • Compare the toxic effects in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study followed by an open-label study. Patients are stratified according to ECOG performance status (0-1 vs 2), prior skeletal-related event (no vs yes), and serum alkaline phosphatase (< upper limit of normal [ULN] vs ≥ ULN). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive zoledronate IV over 15 minutes on day 1.
  • Arm II: Patients receive placebo IV over 15 minutes on day 1. In both arms, courses repeat every 4 weeks in the absence of disease progression or a skeletal-related event. All patients receive concurrent androgen deprivation therapy. Patients also receive oral calcium and cholecalciferol (vitamin D) supplements daily.

Patients progressing to androgen-independent prostate cancer proceed to open-label therapy comprising zoledronate IV over 15 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or a skeletal-related event.

Patients are followed periodically for approximately 10 years after randomization.

PROJECTED ACCRUAL: A total of 680 patients (340 per treatment arm) will be accrued for this study within 4 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate
  • No small cell, neuroendocrine, or transitional cell carcinomas
  • At least 1 bone metastasis by bone scan, MRI, CT scan, or plain radiographs

    • Indeterminate lesions should be confirmed by a second imaging method
    • At least 1 bone metastasis with no prior irradiation
  • Concurrent androgen deprivation therapy required, defined as any of the following:

    • Bilateral orchiectomy
    • Gonadotropin-releasing hormone (GnRH) agonist with or without an antiandrogen

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Creatinine clearance ≥ 30 mL/min
  • Corrected calcium ≥ 8.0 mg/dL and < 11.6 mg/dL

Other

  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Concurrent standard biologic response modifiers allowed during open-label therapy only

Chemotherapy

  • Concurrent standard cytotoxic chemotherapy allowed during open-label therapy only

Endocrine therapy

  • See Disease Characteristics
  • Prior neoadjuvant and/or adjuvant hormonal therapy allowed provided duration of therapy was no more than 6 months AND therapy was discontinued more than 6 months before study entry
  • No more than 6 months since initiation of any of the following hormonal therapies:

    • Orchiectomy
    • GnRH agonist (e.g., leuprolide, goserelin, or triptorelin)
    • Estrogen therapy
    • Antiandrogens (e.g., bicalutamide, flutamide, or nilutamide)
    • Any other therapy known to lower testosterone levels or inhibit testosterone effect
  • No intermittent androgen deprivation therapy except for patients concurrently enrolled on SWOG-9346
  • Concurrent palliative corticosteroids allowed during open-label therapy only
  • Concurrent standard hormonal agents allowed during open-label therapy only

Radiotherapy

  • See Disease Characteristics
  • No prior radiopharmaceuticals
  • At least 4 weeks since prior radiotherapy
  • Concurrent standard radiotherapy to extraskeletal and/or skeletal tumor sites allowed during open-label therapy only

Surgery

  • See Disease Characteristics

Other

  • No prior bisphosphonates
  • No other concurrent agents expected to alter osteoclast activity (e.g., calcitonin, mithramycin, gallium nitrate, or any other bisphosphonate)
  • Concurrent daily supplemental elemental calcium (500 mg) and a multivitamin containing cholecalciferol (Vitamin D) (400 IU) OR a combination tablet containing both recommended
  • Concurrent standard marketed antineoplastic therapies allowed during open-label therapy only
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00079001

  Show 251 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Southwest Oncology Group
Eastern Cooperative Oncology Group
National Cancer Institute of Canada
Investigators
Study Chair: Matthew R. Smith, MD Massachusetts General Hospital
Study Chair: Nirmala Bhoopalam, MD Veterans Affairs Medical Center - Hines
Study Chair: Christopher Sweeney, MBBS Indiana University Melvin and Bren Simon Cancer Center
Study Chair: Fred Saad, MD, FRCS CHUM - Hotel Dieu Hospital
  More Information

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

Study ID Numbers: CDR0000353209, CALGB-90202, ECOG-CALGB-90202, SWOG-CALGB-90202, CAN-NCIC-PRC2
Study First Received: March 8, 2004
Last Updated: January 15, 2009
ClinicalTrials.gov Identifier: NCT00079001  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer
bone metastases

Study placed in the following topic categories:
Zoledronic acid
Prostatic Diseases
Genital Neoplasms, Male
Neoplasm Metastasis
Urogenital Neoplasms
Genital Diseases, Male
Adenocarcinoma
Prostatic Neoplasms
Recurrence

Additional relevant MeSH terms:
Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Physiological Effects of Drugs
Bone Density Conservation Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009