Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, recurrent prostate cancer, stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, stage IV prostate cancer
Brief summary
RATIONALE: Vitamin D may be effective in treating patients with prostate cancer. PURPOSE: This randomized phase II trial is studying how well 4 different doses of vitamin D works in treating patients with prostate cancer.
Detailed description
OBJECTIVES: Primary * To examine the pattern of response of serum 25(OH) D3 levels following cholecalciferol (vitamin D3) supplementation at four different oral doses in patients with prostate cancer. Secondary * To examine the pattern of response of parathormone (PTH) following vitamin D3 supplementation in these patients. * To assess the toxicity of vitamin D3 supplementation in men with prostate cancer. Tertiary * To track occurrence of infections, deep vein thrombosis, vascular events, and falls in these patients. OUTLINE: Patients are randomized to 1 of 4 treatment arms. * Arm I: Patients receive 4,000 IU of oral cholecalciferol (vitamin D3) once daily. * Arm II: Patients receive 6,000 IU of vitamin D3 once daily. * Arm III: Patients receive 8,000 IU of vitamin D3 once daily. * Arm IV: Patients receive 10,000 IU of vitamin D3 once daily. Treatment in all arms continues for 6 months in the absence of disease progression or unacceptable toxicity.
Interventions
DIETARY_SUPPLEMENTcholecalciferol
Given orally
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the prostate * 25(OH) D3 level \< 80 ng/mL PATIENT CHARACTERISTICS: Inclusion criteria: * ECOG performance status 0-2 * Creatinine ≤ 2.0 mg/dL * Corrected serum calcium ≤ 10.5 mg/dL
Exclusion criteria
* History of malabsorption syndrome (e.g., pancreatic insufficiency, celiac disease, or tropical sprue) * Hypersensitivity to cholecalciferol or one of its components PRIOR CONCURRENT THERAPY: * No other concurrent vitamin D supplementation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pattern of Response of Serum 25(OH) D3 Levels | Baseline, at 1, 3, 6 months | Change from Baseline in Serum 25(OH) D3 Levels at 1, 3, and 6 Months at dose levels 4000, 6000, 8000 and 10000 IU. Statistical analysis was done using one sample t-test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pattern of Response of Parathormone | Baseline, at 1, 3, 6 months | Change from Baseline in PTH Levels at 1, 3, and 6 Months at dose levels 4000, 6000, 8000 and 10000 IU. Statistical analysis was done using one sample t-test. |
| Toxicity | Baseline, at 1, 3 and 6 months | Number of treated patients that had serious adverse events. |
| Occurrence of Infections, Deep Vein Thrombosis, Vascular Events, and Falls | Baseline, at 1, 3 ,6 months | Number of participant with occurrence of infections, deep venous thrombosis, vascular events and falls |
Countries
United States
Participant flow
Pre-assignment details
Total 148 patients were treated but only 128 patients were eligible for study outcome analysis.
Participants by arm
| Arm | Count |
|---|---|
| Arm I: Vitamin D 4000 IU Daily Patients receive 4,000 IU of oral cholecalciferol (vitamin D3) once daily.
cholecalciferol: Given orally | 37 |
| Arm II: Vitamin D 6000 IU Daily Patients receive 6,000 IU of vitamin D3 once daily.
cholecalciferol: Given orally | 35 |
| Arm III: Vitamin D 8000 IU Daily Patients receive 8,000 IU of vitamin D3 once daily.
cholecalciferol: Given orally | 36 |
| Arm IV: Vitamin D 10,000 IU Daily Patients receive 10,000 IU of vitamin D3 once daily.
cholecalciferol: Given orally | 40 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 1 |
| Overall Study | Other | 0 | 1 | 2 | 3 |
| Overall Study | progression | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Arm I: Vitamin D 4000 IU Daily | Arm II: Vitamin D 6000 IU Daily | Arm III: Vitamin D 8000 IU Daily | Arm IV: Vitamin D 10,000 IU Daily | Total |
|---|---|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 8.1 | 65.4 years STANDARD_DEVIATION 8.7 | 67.9 years STANDARD_DEVIATION 8.7 | 66.4 years STANDARD_DEVIATION 9.3 | 66.5 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 37 Participants | 35 Participants | 36 Participants | 40 Participants | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 37 | 3 / 35 | 3 / 36 | 9 / 40 |
| serious Total, serious adverse events | 2 / 37 | 0 / 35 | 1 / 36 | 5 / 40 |
Outcome results
Primary
Pattern of Response of Serum 25(OH) D3 Levels
Change from Baseline in Serum 25(OH) D3 Levels at 1, 3, and 6 Months at dose levels 4000, 6000, 8000 and 10000 IU. Statistical analysis was done using one sample t-test.
Time frame: Baseline, at 1, 3, 6 months
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I: Vitamin D 4000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 1-month | 11.34 ng/mL | Standard Deviation 13.03 |
| Arm I: Vitamin D 4000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 6-month | 27.16 ng/mL | Standard Deviation 15.69 |
| Arm I: Vitamin D 4000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 3-month | 23.45 ng/mL | Standard Deviation 11.99 |
| Arm II: Vitamin D 6000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 1-month | 24.84 ng/mL | Standard Deviation 16.18 |
| Arm II: Vitamin D 6000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 6-month | 43.4 ng/mL | Standard Deviation 29.28 |
| Arm II: Vitamin D 6000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 3-month | 38.31 ng/mL | Standard Deviation 22.24 |
| Arm III: Vitamin D 8000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 3-month | 35.76 ng/mL | Standard Deviation 26.28 |
| Arm III: Vitamin D 8000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 1-month | 18.87 ng/mL | Standard Deviation 22.25 |
| Arm III: Vitamin D 8000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 6-month | 41.7 ng/mL | Standard Deviation 27.07 |
| Arm IV: Vitamin D 10,000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 1-month | 26.91 ng/mL | Standard Deviation 16.1 |
| Arm IV: Vitamin D 10,000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 6-month | 57.59 ng/mL | Standard Deviation 27.91 |
| Arm IV: Vitamin D 10,000 IU Daily | Pattern of Response of Serum 25(OH) D3 Levels | 3-month | 45.67 ng/mL | Standard Deviation 21.5 |
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 6-Month for dose level 10000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 1-Month for dose level 4000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 3-Month for dose level 4000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 6-Month for dose level 4000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 1-Month for dose level 6000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 3-Month for dose level 6000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 6-Month for dose level 6000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 1-Month for dose level 8000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 3-Month for dose level 8000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 6-Month for dose level 8000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 1-Month for dose level 10000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in Serum 25(OH) D3 Levels at 3-Month for dose level 10000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Secondary
Occurrence of Infections, Deep Vein Thrombosis, Vascular Events, and Falls
Number of participant with occurrence of infections, deep venous thrombosis, vascular events and falls
Time frame: Baseline, at 1, 3 ,6 months
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Vitamin D 4000 IU Daily | Occurrence of Infections, Deep Vein Thrombosis, Vascular Events, and Falls | 2 participants |
| Arm II: Vitamin D 6000 IU Daily | Occurrence of Infections, Deep Vein Thrombosis, Vascular Events, and Falls | 0 participants |
| Arm III: Vitamin D 8000 IU Daily | Occurrence of Infections, Deep Vein Thrombosis, Vascular Events, and Falls | 2 participants |
| Arm IV: Vitamin D 10,000 IU Daily | Occurrence of Infections, Deep Vein Thrombosis, Vascular Events, and Falls | 2 participants |
Secondary
Pattern of Response of Parathormone
Change from Baseline in PTH Levels at 1, 3, and 6 Months at dose levels 4000, 6000, 8000 and 10000 IU. Statistical analysis was done using one sample t-test.
Time frame: Baseline, at 1, 3, 6 months
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I: Vitamin D 4000 IU Daily | Pattern of Response of Parathormone | 1-month | -.73 pg/mL | Standard Deviation 18.82 |
| Arm I: Vitamin D 4000 IU Daily | Pattern of Response of Parathormone | 6-month | -8.4 pg/mL | Standard Deviation 33.05 |
| Arm I: Vitamin D 4000 IU Daily | Pattern of Response of Parathormone | 3-month | -11.3 pg/mL | Standard Deviation 37.99 |
| Arm II: Vitamin D 6000 IU Daily | Pattern of Response of Parathormone | 1-month | -12.18 pg/mL | Standard Deviation 43.33 |
| Arm II: Vitamin D 6000 IU Daily | Pattern of Response of Parathormone | 6-month | -24.05 pg/mL | Standard Deviation 26.77 |
| Arm II: Vitamin D 6000 IU Daily | Pattern of Response of Parathormone | 3-month | .24 pg/mL | Standard Deviation 34.01 |
| Arm III: Vitamin D 8000 IU Daily | Pattern of Response of Parathormone | 3-month | -8.03 pg/mL | Standard Deviation 32.77 |
| Arm III: Vitamin D 8000 IU Daily | Pattern of Response of Parathormone | 1-month | -1.28 pg/mL | Standard Deviation 31.84 |
| Arm III: Vitamin D 8000 IU Daily | Pattern of Response of Parathormone | 6-month | -9.78 pg/mL | Standard Deviation 34.22 |
| Arm IV: Vitamin D 10,000 IU Daily | Pattern of Response of Parathormone | 1-month | -10.37 pg/mL | Standard Deviation 46.24 |
| Arm IV: Vitamin D 10,000 IU Daily | Pattern of Response of Parathormone | 6-month | -16.51 pg/mL | Standard Deviation 45.94 |
| Arm IV: Vitamin D 10,000 IU Daily | Pattern of Response of Parathormone | 3-month | -18.06 pg/mL | Standard Deviation 35.31 |
Comparison: Change from Baseline in PTH Levels at 1-month for 4000 IU. Statistical analysis was done using one sample t-test.p-value: 0.8244t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 3-month for 4000 IU. Statistical analysis was done using one sample t-test.p-value: 0.1025t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 6-Month for dose level 4000 IU.p-value: 0.1744t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 1-month for 6000 IU. Statistical analysis was done using one sample t-test.p-value: 0.1281t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 3-month for 6000 IU. Statistical analysis was done using one sample t-test.p-value: 0.9688t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 6-month for 6000 IU. Statistical analysis was done using one sample t-test.p-value: <0.0001t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 1-month for 8000 IU. Statistical analysis was done using one sample t-test.p-value: 0.8241t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 3-month for 8000 IU. Statistical analysis was done using one sample t-test.p-value: 0.1828t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 6-month for 8000 IU. Statistical analysis was done using one sample t-test.p-value: 0.1348t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 1-month for 10000 IU. Statistical analysis was done using one sample t-test.p-value: 0.2214t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 3-month for 10000 IU. Statistical analysis was done using one sample t-test.p-value: 0.0079t-test, 2 sided
Comparison: Change from Baseline in PTH Levels at 6-month for 10000 IU. Statistical analysis was done using one sample t-test.p-value: 0.0631t-test, 2 sided
Secondary
Toxicity
Number of treated patients that had serious adverse events.
Time frame: Baseline, at 1, 3 and 6 months
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Vitamin D 4000 IU Daily | Toxicity | 2 participants |
| Arm II: Vitamin D 6000 IU Daily | Toxicity | 0 participants |
| Arm III: Vitamin D 8000 IU Daily | Toxicity | 1 participants |
| Arm IV: Vitamin D 10,000 IU Daily | Toxicity | 5 participants |