High-Dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients

• ClinicalTrials.gov Identifier: NCT05838716
• Recruitment Status: Recruiting
• First Posted: May 1, 2023
• Last Update Posted: January 18, 2024
• Sponsor: University of Rochester NCORP Research Base
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Luke Peppone, University of Rochester NCORP Research Base

Tracking Information

• First Submitted Date: April 20, 2023
• First Posted Date: May 1, 2023
• Last Update Posted Date: January 18, 2024
• Actual Study Start Date: December 14, 2023
• Estimated Primary Completion Date: May 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 20, 2023)

• Reduction of bone mineral density (BMD) loss as measured at the total hip [ Time Frame: 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 via dual-energy x-ray absorptiometry (DXA) at 52 weeks. Will use analysis of variance (ANCOVA) with Group (vitamin D or placebo) as the main factor, baseline BMD as covariate, and T3 (week 52) 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 lumbar spine [ Time Frame: At 52 weeks ]
  Will determine the efficacy of HDVD supplementation versus placebo in reducing BMD loss as measured at the lumbar spine total via DXA at 52 weeks. Will use ANCOVA with Group (vitamin D or placebo) as the main factor, baseline BMD as covariate, and T3 (week 52) 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High-Dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients
• Official Title: High-dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients
• Brief Summary: This phase III trial tests whether high-dose vitamin D works in treating androgen-deprivation therapy (ADT)-induced bone loss in patients with prostate cancer who are undergoing androgen-deprivation therapy. Vitamins are substances that the body needs to grow and develop normally. Vitamin D helps the body absorb calcium. Calcium is one of the main building blocks of bone. A lack of vitamin D can lead to bone diseases such as osteoporosis or rickets. This trial may help researcher determine if high-dose vitamin D helps keep bones strong, lowers number of falls, and lessens fatigue in men getting androgen-deprivation therapy.

Detailed Description

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 OBJECTIVES:

I. To explore the effect of HDVD supplementation on skeletal muscle mass as measured by DXA.

II. To explore the effect of HDVD supplementation on bone biomarkers measured by Millipore Luminex/enzyme-linked immunosorbent assay (ELISA) assays from serum.

III. 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, patents are randomized to 1 of 2 arms.

ARM I: Patients receive HDVD orally (PO) throughout the study. Patients also undergo collection of blood and DXA scan on study.

ARM II: Patients receive placebo PO throughout the study. Patients also undergo collection of blood and DXA scan on study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator); Primary Purpose: Supportive Care

Condition

• Stage I Prostate Cancer AJCC v8
• Stage II Prostate Cancer AJCC v8
• Stage III Prostate Cancer AJCC v8
• Stage IVA Prostate Cancer AJCC v8

Intervention

• Procedure: Biospecimen Collection
  Undergo collection of blood
  Other Names:

  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
• Dietary Supplement: D Vitamin
  Given PO
  Other Names:

  • 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
• Procedure: Dual X-ray Absorptiometry
  Undergo DXA scan
  Other Names:

  • 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
• Drug: Placebo Administration
  Given PO
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Other: Questionnaire Administration
  Ancillary studies

Study Arms

• Experimental: Arm I (HDVD)
  Patients receive HDVD PO throughout the study. Patients also undergo collection of blood and DXA scan on study.
  Interventions:

  • Procedure: Biospecimen Collection
  • Dietary Supplement: D Vitamin
  • Procedure: Dual X-ray Absorptiometry
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
• Placebo Comparator: Arm II (placebo, DXA scan, blood collection, questionnaire)
  Patients receive placebo PO throughout the study. Patients also undergo collection of blood and DXA scan on study.
  Interventions:

  • Procedure: Biospecimen Collection
  • Procedure: Dual X-ray Absorptiometry
  • Drug: Placebo Administration
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 20, 2023): 366
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2027
• Estimated Primary Completion Date: May 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 60 years or older
• Be starting ADT or have received their first ADT treatment in the past 3 months, with at least 6 planned months of treatment remaining (both luteinizing hormone-releasing hormone (LHRH) antagonists and LHRH agonists are permitted)
• Have a total serum vitamin D between 10 and 27 ng/ml
• Have an total serum calcium of less than or equal to 10.5 mg/dl
• Have a normal GFR (glomerular filtration rate)
• 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 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 10.5 mg/dl)
• Have a history of hypercalcemia or vitamin D toxicity/sensitivity

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Olivia Tauriello; 585-275-8507; Olivia_Tauriello@URMC.Rochester.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05838716
• Other Study ID Numbers: URCC-22053; NCI-2022-07664 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); URCC-22053 ( Other Identifier: University of Rochester NCORP Research Base ); URCC-22053 ( Other Identifier: DCP ); URCC-22053 ( Other Identifier: CTEP ); R01CA258349 ( U.S. NIH Grant/Contract ); UG1CA189961 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Luke Peppone, University of Rochester NCORP Research Base
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Rochester NCORP Research Base
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Luke J Peppone; University of Rochester NCORP Research Base

• PRS Account: University of Rochester
• Verification Date: January 2024