Vitamin D for Prostate Endocrine Therapy

PRIMARY OBJECTIVES:

I. To evaluate the effect of high-dose vitamin D (HDVD) supplementation in prostate cancer patients on ADT-induced bone mineral density loss in the total hip over 52 weeks as measured by dual-energy x-ray absorptiometry (DXA).

II. To evaluate the effect of HDVD supplementation in prostate cancer patients on ADT-induced bone mineral density loss in the femoral neck, distal radius, and lumbar spine (L1-L4) over 52 weeks as measured by DXA.

SECONDARY OBJECTIVES:

I. To evaluate the effect of HDVD supplementation on falls over 52 weeks as measured by the Falls History questionnaire.

II. To evaluate the effect of HDVD supplementation on fractures over 52 weeks as determined by the Clinical Record Information - Follow-up Form.

III. To evaluate the effect of HDVD supplementation on quality of life over 52 weeks as measured by the Functional Assessment of Cancer Therapy- Prostate (FACT-P).

EXPLORATORY OBJECTIVE:

I. To evaluate the effect of HDVD supplementation on pain, fatigue, sleep, and activities of daily living over 52 weeks as measured by patient-reported outcomes.

OUTLINE: After undergoing collection of blood and DXA scan, patients are randomized to 1 of 2 arms.

ARM I: Patients receive HDVD orally (PO) once a week (QW) for 52 weeks. Patients also undergo collection of blood and DXA scan on study.

ARM II: Patients receive placebo PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study.

• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo collection of blood
• D Vitamin (Dietary supplement), also known as 3-[2-[7a-methyl-1-(1,4,5-trimethylhex-2-enyl)-1,2,3,3a,5,6,7,7a-octahydroinden-4-ylidene]ethylidene]-4-methylidene-cyclohexan-1-ol, Vitamin D, Vitamin D Compound, Vitamin-D: Given PO
• Dual X-ray Absorptiometry (Procedure), also known as BMD scan, bone mineral density scan, DEXA, DEXA (Bone Density), DEXA Scan, dual energy x-ray absorptiometric scan, Dual Energy X-ray Absorptiometry, Dual X-Ray Absorptometry, DXA, DXA SCAN: Undergo DXA scan
• Placebo Administration (Drug): Given PO
• Quality-of-Life Assessment (Other), also known as Quality of Life Assessment: Ancillary studies
• Questionnaire Administration (Other): Ancillary studies

Primary outcomes

• Reduction of bone mineral density (BMD) loss as measured at the total hip [At 52 weeks]: Will determine the efficacy of high-dose vitamin D (HDVD) supplementation versus placebo in reducing BMD loss as measured at the total hip via dual-energy x-ray absorptiometry (DXA) at 52 weeks. Will use analysis of covariance (ANCOVA) with group (vitamin D or placebo) as the main factor, baseline timepoint (\[T\]1) BMD as covariate, and week 52 (T3) BMD as the outcome. Study site will be included as a random effect independent of residual error. An initial linear mixed model (LMM) will be fit using Restricted Maximum Likelihood (REML) estimation. The significance of the variance due to study site will be tested using the Wald Test.
• Reduction of BMD loss as measured at the femoral neck [At 52 weeks]: Will determine the efficacy of HDVD supplementation versus placebo in reducing BMD loss as measured at the femoral neck via DXA at 52 weeks. Will use ANCOVA with group (vitamin D or placebo) as the main factor, baseline (T1) BMD as covariate, and week 52 (T3) BMD as the outcome. Study site will be included as a random effect independent of residual error. An initial LMM will be fit using REML estimation. The significance of the variance due to study site will be tested using the Wald Test.
• Reduction of BMD loss as measured at the distal radius [At 52 weeks]: Will determine the efficacy of HDVD supplementation versus placebo in reducing BMD loss as measured at the distal radius via DXA at 52 weeks. Will use ANCOVA with group (vitamin D or placebo) as the main factor, baseline (T1) BMD as covariate, and week 52 (T3) BMD as the outcome. Study site will be included as a random effect independent of residual error. An initial LMM will be fit using REML estimation. The significance of the variance due to study site will be tested using the Wald Test.
• Reduction of BMD loss as measured at the lumbar spine [At 52 weeks]: Will determine the efficacy of HDVD supplementation versus placebo in reducing BMD loss as measured at the lumbar spine via DXA at 52 weeks. Will use ANCOVA with group (vitamin D or placebo) as the main factor, baseline (T1) BMD as covariate, and week 52 (T3) BMD as the outcome. Study site will be included as a random effect independent of residual error. An initial LMM will be fit using REML estimation. The significance of the variance due to study site will be tested using the Wald Test.

Secondary outcomes

• Change in falls [Baseline up to 52 weeks]: Will use generalized linear mixed models. Logistic regression models will be used to estimate the between group difference in (1) the proportion of participants who experience a fall/fracture (YES/NO) from T1 to T3. Will evaluate the distribution of total number of falls/fractures by Poisson models analysis to estimate the between group difference in (2) the total number of falls/fractures from T1 to T3. Both models (1, 2) will contain group as fixed effect and site as a random effect. Additional adjustment covariates will include falls in the previous 6 months, fractures in the previous 5 years, androgen-deprivation therapy (ADT) dose and duration, stage, radiation therapy, prior surgery, baseline vitamin D, age, body mass index (BMI), and race. Nonsignificant (P > 0.05) covariates will be removed from the model. Will report the estimates and associated 95% confidence intervals as (1) relative risk or (2) rate ratio.
• Change in fractures [Baseline up to 52 weeks]: Will use generalized linear mixed models. Logistic regression models will be used to estimate the between group difference in (1) the proportion of participants who experience a fall/fracture (YES/NO) from T1 to T3. Will evaluate the distribution of total number of falls/fractures by Poisson models analysis to estimate the between group difference in (2) the total number of falls/fractures from T1 to T3. Both models (1, 2) will contain group as fixed effect and site as a random effect. Additional adjustment covariates will include falls in the previous 6 months, fractures in the previous 5 years, ADT dose and duration, stage, radiation therapy, prior surgery, baseline vitamin D, age, BMI, and race. Nonsignificant (P > 0.05) covariates will be removed from the model. Will report the estimates and associated 95% confidence intervals as (1) relative risk or (2) rate ratio.
• Change in quality of life [Baseline up to 52 weeks]: Will be evaluated by Functional Assessment of Cancer Therapy-Prostate Trial Outcome Index score.

Sex: Male, ages: 50 Years to any

Inclusion Criteria:

* Be diagnosed with Stage I-IV prostate cancer without metastases to bone (lymph node involvement and prior diagnosis of a primary cancer is allowed)
* Be age 50 years or older
* Be starting ADT or have received their first ADT treatment in the past 6 months, with a total of at least 6 planned months of treatment (both luteinizing hormone-releasing hormone \[LHRH\] antagonists and LHRH agonists are permitted)
* Have a total serum vitamin D between 10 and 32 ng/ml
* Have a total serum calcium of less than or equal to 10.5 mg/dl
* Have a normal GFR (glomerular filtration rate > 30ml)
* Agree not to take calcium and/or vitamin D supplements for the duration of the intervention other than those provided by the study
* Be able to provide written informed consent
* Be able to swallow pills and capsules
* Be able to speak and read English

Exclusion Criteria:

* Have long term (greater than 3 months) use of any pharmacologic bone-modifying agent including but not limited to oral or intravenous (IV) bisphosphonates, denosumab, or teriparatide prior to enrollment
* Have a diagnosis of stage IV chronic kidney disease
* Have a diagnosis of grade II or greater hypercalcemia (serum calcium greater than 11.5 mg/dl)
* Have a history of hypercalcemia or vitamin D toxicity/sensitivity

• Luke J Peppone, Principal investigator, University of Rochester NCORP Research Base

NIH grants: R01CA258349, UG1CA189961