Prostate Adenocarcinoma
Conditions
Brief summary
This randomized clinical trial studies how well cholecalciferol supplement works in treating patients with localized prostate cancer undergoing observation. Cholecalciferol may help prostate cancer cells become more like normal cells, and to grow and spread more slowly.
Detailed description
PRIMARY OBJECTIVES: I. To determine the prostate-specific antigen (PSA) response with oral high dose vitamin D3 supplementation (cholecalciferol) in patients with localized, histologically proven adenocarcinoma of the prostate who have not received any treatment for prostate cancer ever and have chosen expectant management. SECONDARY OBJECTIVES: I. To examine the pattern of response of PSA dynamics as well as the absolute change in PSA following vitamin D3 supplementation. II. Assess the toxicity of vitamin D3 supplementation in men with prostate cancer. TERTIARY OBJECTIVES: I. Track occurrence of infections, deep venous thrombosis, vascular events and falls in the study population. II. To evaluate relationship between cytochrome P450 family 24 (CYP24), 27B1, single-nucleotide polymorphism (SNPs) and serum 25(hydroxy \[OH\]) vitamin D response to oral D3 supplementation. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cholecalciferol orally (PO) once daily (QD) for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Arm II. ARM II: Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Arm I. After completion of study treatment, patients are followed up for 30 days.
Interventions
DIETARY_SUPPLEMENTCholecalciferol
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPatient Observation
DRUGPlacebo Administration
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Roswell Park Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Any patient with clinically localized, histologically proven adenocarcinoma of prostate who has not received any treatment for prostate cancer ever and has chosen active surveillance; treatment for prostate cancer is defined as prostatectomy, androgen deprivation, brachytherapy or a full course of external beam irradiation * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Willingness to comply with study guidelines * Willingness and ability to consent * 25(OH) D3 level less than 40 ng/ml within 3 months of initiation of study; most recent 25 hydroxy D level within last 3 month would be used
Exclusion criteria
* History of malabsorption syndrome e.g., pancreatic insufficiency, celiac disease, tropical sprue * Creatinine \> 2.0 mg/dL * Corrected serum calcium level of \> 10.5 mg/dL (serum corrected calcium = serum calcium + 0.8\[4-serum albumin\]) * Most recent PSA value more than 18 months ago * Prior or current therapy for prostate cancer * Documented history of nephrolithiasis within the past 5 years * Patients receiving finasteride (Proscar) or dutasteride (Avodart) or men who have received either agent within 90 days of entry are ineligible * Patients cannot take any additional vitamin D supplementation during study treatment; patients taking \> 2000 IU per day prior to treatment will be ineligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response | 9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment | Difference in the mean change in PSA on vitamin D (9 month period: pre-Vitamin D to 9 months after start of vitamin D) versus on placebo (9 month period: pre-Placebo to 9 months after starting placebo). Compared using a paired t-test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Slope of PSA Concentration Over Time | 9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment -Up to 30 days after completion of study treatment | The PSA levels were modeled as a function of treatment, time, their interaction, sequence, and a random subject effect using a linear mixed model. From this model, the subject specific PSA slope was obtained for each subject under each condition (vitamin D versus placebo). The PSA slopes were then compared between treatment conditions using linear mixed model to account for treatment arm and repeated measures. |
| Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Up to 30 days after completion of study treatment (up to 22 months from start of study). | Summarizing the maximum observed treatment related adverse event. Summarize by arm and grade using frequencies and relative frequencies.. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Cholecalciferol and Placebo) Patients receive cholecalciferol PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to placebo PO QD for 9 months.
Cholecalciferol: Given PO
Laboratory Biomarker Analysis: Correlative studies
Patient Observation
Placebo Administration: Given PO
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies | 58 |
| Arm II (Placebo and Cholecalciferol) Patients receive placebo PO QD for 9 months in the absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to cholecalciferol PO QD for 9 months.
Cholecalciferol: Given PO
Laboratory Biomarker Analysis: Correlative studies
Patient Observation
Placebo Administration: Given PO
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies | 74 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not complete treatment | 6 | 8 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | No reason provided | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Start Excluded Therapy | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Arm I (Cholecalciferol and Placebo) | Arm II (Placebo and Cholecalciferol) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 25 Participants | 39 Participants | 64 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants | 35 Participants | 68 Participants |
| Age, Continuous | 63.5 years STANDARD_DEVIATION 7 | 64.9 years STANDARD_DEVIATION 6.5 | 64.3 years STANDARD_DEVIATION 6.8 |
| Prostate Specific Antigen (PSA) | 5.2 ng/mL STANDARD_DEVIATION 2.9 | 4.8 ng/mL STANDARD_DEVIATION 2.6 | 5.0 ng/mL STANDARD_DEVIATION 2.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 50 Participants | 69 Participants | 119 Participants |
| Region of Enrollment United States | 58 Participants | 74 Participants | 132 Participants |
| Serum 25(OH)D3 | 25.1 ng/mL STANDARD_DEVIATION 10.7 | 30.4 ng/mL STANDARD_DEVIATION 9 | 27.9 ng/mL STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 58 Participants | 74 Participants | 132 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 119 | 0 / 120 |
| other Total, other adverse events | 2 / 119 | 2 / 120 |
| serious Total, serious adverse events | 0 / 119 | 0 / 120 |
Outcome results
Primary
PSA Response
Difference in the mean change in PSA on vitamin D (9 month period: pre-Vitamin D to 9 months after start of vitamin D) versus on placebo (9 month period: pre-Placebo to 9 months after starting placebo). Compared using a paired t-test.
Time frame: 9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment
Population: Patients who completed both periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | PSA Response | 0.55 ng/mL | Standard Deviation 2.13 |
| Placebo | PSA Response | 0.31 ng/mL | Standard Deviation 1.86 |
Comparison: Evaluated the change in PSA under the vitamin D and placebo conditions using the combined data (n=87).p-value: 0.43195% CI: [-0.36, 0.84]t-test, 2 sided
Secondary
Slope of PSA Concentration Over Time
The PSA levels were modeled as a function of treatment, time, their interaction, sequence, and a random subject effect using a linear mixed model. From this model, the subject specific PSA slope was obtained for each subject under each condition (vitamin D versus placebo). The PSA slopes were then compared between treatment conditions using linear mixed model to account for treatment arm and repeated measures.
Time frame: 9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment -Up to 30 days after completion of study treatment
Population: Including evaluable patients, those patients with data available under both the vitamin D and placebo conditions.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Slope of PSA Concentration Over Time | 0.000434 (ng/mL) / day | Standard Error 0.000089 |
| Placebo | Slope of PSA Concentration Over Time | 0.000245 (ng/mL) / day | Standard Error 0.00009 |
p-value: 0.11295% CI: [-0.00042, 0.000045]Mixed Models Analysis
Secondary
Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Summarizing the maximum observed treatment related adverse event. Summarize by arm and grade using frequencies and relative frequencies..
Time frame: Up to 30 days after completion of study treatment (up to 22 months from start of study).
Population: All patients receiving any treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cholecalciferol | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 2 | 0 Participants |
| Cholecalciferol | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 3 | 1 Participants |
| Cholecalciferol | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 4 | 0 Participants |
| Cholecalciferol | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 1 | 1 Participants |
| Cholecalciferol | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 5 | 0 Participants |
| Cholecalciferol | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | No AE | 117 Participants |
| Placebo | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 5 | 0 Participants |
| Placebo | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | No AE | 118 Participants |
| Placebo | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 1 | 2 Participants |
| Placebo | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 3 | 0 Participants |
| Placebo | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 4 | 0 Participants |
| Placebo | Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Grade 2 | 0 Participants |