Zoledronate in Preventing Skeletal (Bone)-Related Events in Patients Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Southwest Oncology Group
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079001
First received: March 8, 2004
Last updated: September 6, 2012
Last verified: July 2012
  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: zoledronic acid
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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
Placebo Comparator: Arm II
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.
Other: 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 tumor sites allowed during open-label therapy only

Surgery

  • See Disease Characteristics

Other

  • No prior bisphosphonates
  • No prior denosumab
  • No other concurrent agents expected to alter osteoclast activity (e.g., denosumab, 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 241 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Southwest Oncology Group
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
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

Additional Information:
No publications provided

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00079001     History of Changes
Obsolete Identifiers: NCT00698308
Other Study ID Numbers: CDR0000353209, CALGB-90202, ECOG-CALGB-90202, SWOG-CALGB-90202, CAN-NCIC-PRC2
Study First Received: March 8, 2004
Last Updated: September 6, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Prostatic Neoplasms
Neoplastic Processes
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014