High-Dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients
- Conditions
- Stage I Prostate Cancer AJCC v8Stage II Prostate Cancer AJCC v8Stage III Prostate Cancer AJCC v8Stage IVA Prostate Cancer AJCC v8
- Interventions
- Procedure: Biospecimen CollectionDietary Supplement: D VitaminProcedure: Dual X-ray AbsorptiometryDrug: Placebo AdministrationOther: Quality-of-Life AssessmentOther: Questionnaire Administration
- Registration Number
- NCT05838716
- Lead Sponsor
- University of Rochester NCORP Research Base
- 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 researchers 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 bone biomarkers measured by Millipore Luminex/enzyme-linked immunosorbent assay (ELISA) assays from serum.
II. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 366
- 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 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 27 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (HDVD) Biospecimen Collection Patients receive HDVD PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm I (HDVD) D Vitamin Patients receive HDVD PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm I (HDVD) Dual X-ray Absorptiometry Patients receive HDVD PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm I (HDVD) Quality-of-Life Assessment Patients receive HDVD PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm I (HDVD) Questionnaire Administration Patients receive HDVD PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm II (placebo) Biospecimen Collection Patients receive placebo PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm II (placebo) Dual X-ray Absorptiometry Patients receive placebo PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm II (placebo) Placebo Administration Patients receive placebo PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm II (placebo) Quality-of-Life Assessment Patients receive placebo PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study. Arm II (placebo) Questionnaire Administration Patients receive placebo PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (46)
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
University of Kansas Cancer Center-Overland Park
🇺🇸Overland Park, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸Westwood, Kansas, United States
Louisiana State University Health Science Center
🇺🇸New Orleans, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
University of Kansas Cancer Center - North
🇺🇸Kansas City, Missouri, United States
University of Kansas Cancer Center - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
OptumCare Cancer Care at Charleston
🇺🇸Las Vegas, Nevada, United States
CarolinaEast Medical Center
🇺🇸New Bern, North Carolina, United States
Nash UNC HealthCare
🇺🇸Rocky Mount, North Carolina, United States
Community Medical Center
🇺🇸Scranton, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Gibbs Cancer Center-Gaffney
🇺🇸Gaffney, South Carolina, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
Gibbs Cancer Center-Pelham
🇺🇸Greer, South Carolina, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
SMC Center for Hematology Oncology Union
🇺🇸Union, South Carolina, United States
Regional Cancer Center at Johnson City Medical Center
🇺🇸Johnson City, Tennessee, United States
Ballad Health Cancer Care - Kingsport
🇺🇸Kingsport, Tennessee, United States
Ballad Health Cancer Care - Bristol
🇺🇸Bristol, Virginia, United States
Bon Secours Memorial Regional Medical Center
🇺🇸Mechanicsville, Virginia, United States
Bon Secours Saint Francis Medical Center
🇺🇸Midlothian, Virginia, United States
Bon Secours Saint Mary's Hospital
🇺🇸Richmond, Virginia, United States
Bon Secours Cancer Institute at Reynolds Crossing
🇺🇸Richmond, Virginia, United States
VCU Massey Cancer Center at Stony Point
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Carilion Roanoke Memorial Hospital
🇺🇸Roanoke, Virginia, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
🇺🇸Sturgeon Bay, Wisconsin, United States