Zoledronate in Preventing Skeletal (Bone)-Related Events in Patients Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases
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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 |
- Time to first skeletal related event [ Designated as safety issue: No ]
- 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 |
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
Show 241 Study Locations| 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 May 23, 2013