A Phase 3 interventional study of Calcium and Zoledronic acid in Osteoporosis and Prostate Cancer, sponsored by Radiation Therapy Oncology Group. Completed at 88 sites in 2 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-11-29.
Sponsored by Radiation Therapy Oncology Group · Phase 3, Interventional, and Supportive care
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.
OBJECTIVES:
Primary
Secondary
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.
Quality of life is assessed at baseline and every 6 months during treatment.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.
This study's enrollment of 109 is above the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Radiation Therapy Oncology Group is the lead sponsor of 154 studies on the registry; none are open to participants now.
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Eligibility criteria:
Any one of the following clinical stages:
Ineligibility criteria:
Zoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Dietary Supplement: Calcium · Dietary Supplement: Zoledronic acid · Radiation: radiation therapy · Drug: LHRH · Dietary Supplement: Vitamin D
Vitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Dietary Supplement: Calcium · Radiation: radiation therapy · Drug: LHRH · Dietary Supplement: Vitamin D
A single dose of 500 mg of elemental calcium orally each day for 3 years.
Patients receive IV over 15 minutes once every 6 months for 3 years. The goal dose of zoledronic acid is 4 mg, but the selection of dose is determined based on calculated creatinine clearance at baseline.
Also known as: Zometa, zoledronate
Patients must receive external beam irradiation, brachytherapy (HDR or LDR), or a combination of external beam irradiation and brachytherapy at the discretion of the treating physician. Dose/duration also will be at the discretion of the treating physician; however, dose will not exceed 45 Gy to 100% of the proximal femur, and no proximal femur will receive ≥ 60 Gy.
LHRH therapy must take place for a minimum of one year. Choice of LHRH agonist, dose, and duration are at the discretion of the treating physician.
400 IU (10μg), orally each day for 3 years.
Freedom From Any Bone Fracture (FABF) Rate at Three Years
The time of failure was measured from the date of randomization to the date of documented bone fractures, defined as any fracture of the bone. The three-year FABF rate will be estimated by the Kaplan-Meier method.
Time frame: From randomization to 3 years
Percent Change in Bone Mineral Density at 3 Years
Bone mineral density (BMD) was measured by DXA scan (Dual X-ray absorptiometry) for five locations: lumbar, right total hip, left total hip, right femoral neck, and left femoral neck. The percent change at 3 years was calculated for each location by the following formula: Percent Change BMD = (BMD_3 years - BMD_Baseline)/ BMD_Baseline \* 100.
Time frame: Baseline, 3 years from start of treatment
Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 Years
The FACT-G is a validated, 27-item measure. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, with 0=Not a lot and 4=Very much. All items in a subscale are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range from 0-108 for the FACT-G total score, 0-28 for the physical, social and functional subscales, and 0-24 for the emotional subscale. Certain items, identified on the FACT-G scoring guides, must be reversed before it is added by subtracting the response from 4. All subscale totals are added together to form the FACT-G total score. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing, the subscale scores can be prorated. A higher score indicates better QOL.
Time frame: Baseline, 3 years from start of treatment
Utility of the Use of Bisphosphonates as Assessed by Quality-adjusted Survival
The EQ-5D is a standardized instrument for measuring generic health status used to generate health utilities, used to derive quality adjusted survival. Quality adjusted survival is computed using the weighted sum of times in different health states added up to a total quality-adjusted survival time. The log-rank test is used to compare quality-adjusted survivals between the treatment arms.
Time frame: From pre-treatment to 3 years from start of treatment
| Milestone | Zoledronic Acid | Control |
|---|---|---|
| Started | 57 | 52 |
| Completed | 50 | 46 |
| Not completed | 7 | 6 |
| Withdrew: Protocol violation | 1 | 0 |
| Withdrew: Withdrawal by subject | 6 | 6 |
The time of failure was measured from the date of randomization to the date of documented bone fractures, defined as any fracture of the bone. The three-year FABF rate will be estimated by the Kaplan-Meier method.
| percentage of participants | Zoledronic Acid | Control |
|---|---|---|
| Freedom From Any Bone Fracture (FABF) Rate at Three Years | 98.0 (94.0 to 100.0) | 97.4 (92.3 to 100.0) |
Bone mineral density (BMD) was measured by DXA scan (Dual X-ray absorptiometry) for five locations: lumbar, right total hip, left total hip, right femoral neck, and left femoral neck. The percent change at 3 years was calculated for each location by the following formula: Percent Change BMD = (BMD_3 years - BMD_Baseline)/ BMD_Baseline \* 100.
| percentage of baseline value | Zoledronic Acid | Control |
|---|---|---|
| Lumbar | 6 (-5 to 15) | -5 (-19 to -1) |
| Hip - Right | -2 (-17 to 3) | -5 (-13 to 1) |
| Hip - Left | 1 (-6 to 13) | -8 (-18 to 3) |
| Femoral - Right | 1 (-13 to 4) | -6 (-9 to 0) |
| Femoral - Left | 3 (-8 to 12) | -8 (-26 to 3) |
The FACT-G is a validated, 27-item measure. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, with 0=Not a lot and 4=Very much. All items in a subscale are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range from 0-108 for the FACT-G total score, 0-28 for the physical, social and functional subscales, and 0-24 for the emotional subscale. Certain items, identified on the FACT-G scoring guides, must be reversed before it is added by subtracting the response from 4. All subscale totals are added together to form the FACT-G total score. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing, the subscale scores can be prorated. A higher score indicates better QOL.
| units on a scale | Zoledronic Acid | Control |
|---|---|---|
| Physical Subscale | -1.03 (-15 to 8) | 0.06 (-5 to 10) |
| Social Subscale | -0.69 (-7.00 to 6.42) | -1.13 (-14.7 to 18.00) |
| Emotional Subscale | 1.83 (-4.00 to 10.00) | 1.15 (-4.00 to 14.00) |
| Functional Subscale | -1.10 (-20.8 to 5.00) | -2.76 (-11.0 to 6.00) |
| Total | -1.00 (-30.7 to 19.00) | -2.77 (-27.7 to 27.00) |
The EQ-5D is a standardized instrument for measuring generic health status used to generate health utilities, used to derive quality adjusted survival. Quality adjusted survival is computed using the weighted sum of times in different health states added up to a total quality-adjusted survival time. The log-rank test is used to compare quality-adjusted survivals between the treatment arms.
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Zoledronic Acid | — | 8/50 (16%) | 45/50 (90%) |
| Control | — | 5/46 (10.9%) | 38/46 (82.6%) |
| Event | Zoledronic Acid | Control |
|---|---|---|
| Renal/genitourinary - Other:Renal and urinary disorders | 2/50 | 0/46 |
| Abdominal pain NOSGastrointestinal disorders | 1/50 | 1/46 |
| Death NOSGeneral disorders | 0/50 | 1/46 |
| Gait abnormal NOSGeneral disorders | 0/50 | 1/46 |
| LymphopeniaInvestigations | 0/50 | 1/46 |
| Glucose tolerance impairedMetabolism and nutrition disorders | 0/50 | 1/46 |
| Cerebral ischaemiaNervous system disorders | 0/50 | 1/46 |
| Confusional statePsychiatric disorders | 0/50 | 1/46 |
| Left ventricular failureCardiac disorders | 1/50 | 0/46 |
| Myocardial ischaemiaCardiac disorders | 1/50 | 0/46 |
| Event | Zoledronic Acid | Control |
|---|---|---|
| Hot flushes NOSVascular disorders | 27/50 | 25/46 |
| FatigueGeneral disorders | 23/50 | 15/46 |
| PollakiuriaRenal and urinary disorders | 20/50 | 13/46 |
| HemoglobinBlood and lymphatic system disorders | 13/50 | 11/46 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 13/50 | 7/46 |
| Rectal hemorrhageGastrointestinal disorders | 4/50 | 9/46 |
| Diarrhoea NOSGastrointestinal disorders | 9/50 | 8/46 |
| Erectile dysfunction NOSReproductive system and breast disorders | 9/50 | 6/46 |
| Bone painMusculoskeletal and connective tissue disorders | 8/50 | 2/46 |
| ConstipationGastrointestinal disorders | 7/50 | 4/46 |
Eligible patients
| Age, Continuous(years) | Zoledronic Acid | Control | Total |
|---|---|---|---|
| Median | 70 (51 to 87) | 71 (56 to 84) | 71 (51 to 87) |
| Sex: Female, Male(Participants) | Zoledronic Acid | Control | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 50 | 46 | 96 |
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