High-Dose Vitamin D for Bone Loss in Prostate Cancer

Recruiting at 46 trial locations

Overseen By Brooke Burgess, MS

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: University of Rochester NCORP Research Base

Must be taking: LHRH antagonists, LHRH agonists

Must not be taking: Bisphosphonates, Denosumab, Teriparatide

Disqualifiers: Stage IV kidney disease, Hypercalcemia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

366 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if high-dose vitamin D can prevent bone loss in men undergoing androgen-deprivation therapy (ADT) for prostate cancer. ADT can weaken bones, and researchers seek to find out if vitamin D can maintain bone strength, reduce falls, and lessen fatigue. Participants will receive either high-dose vitamin D (cholecalciferol or ergocalciferol) or a placebo (a pill with no active ingredient) for a year. Men with prostate cancer without bone metastases who have recently started ADT may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop taking my current medications for this trial?

The trial requires that you stop taking any calcium and vitamin D supplements other than those provided by the study. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that high doses of vitamin D can help reduce bone loss in people undergoing certain cancer treatments. In earlier studies, patients who took high doses lost less bone density in areas like the hip, particularly those with initially lower vitamin D levels in their blood.

Vitamin D is generally safe to take, with a safe upper limit for adults set at 4,000 IU per day. Most participants in studies did not experience serious side effects from high doses. However, following the study team's instructions is crucial, as excessive vitamin D can lead to high calcium levels in the blood.

Overall, past research supports that high-dose vitamin D is safe for most people, especially when monitored in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike the standard treatments for bone loss in prostate cancer, which often include bisphosphonates or denosumab, high-dose vitamin D (HDVD) offers a unique approach. Researchers are excited about HDVD because it leverages vitamin D’s potential to enhance bone health by improving calcium absorption and bone mineralization. This treatment is also straightforward, as it's administered orally once a week, which could simplify patient compliance compared to more invasive options. By focusing on a natural nutrient that plays a crucial role in bone metabolism, HDVD has the potential to offer a safer alternative with fewer side effects.

What evidence suggests that high-dose vitamin D might be an effective treatment for bone loss in prostate cancer?

This trial will compare high-dose vitamin D (HDVD) with a placebo to assess its impact on bone loss in patients undergoing androgen-deprivation therapy (ADT) for prostate cancer. Research has shown that high doses of vitamin D can reduce bone loss, significantly slowing the loss of bone density in the hip and upper thigh bone, especially in individuals with initially low vitamin D levels. Vitamin D aids the body's absorption of calcium, which is crucial for maintaining strong bones. While some studies suggest potential risks with high doses, others have found benefits for bone health, particularly when the dosage is tailored to individual needs. ^{1 2 3 6 7}

Who Is on the Research Team?

Luke J Peppone, PhD

Principal Investigator

University of Rochester NCORP Research Base

Are You a Good Fit for This Trial?

This trial is for men aged 60 or older with Stage I-IV prostate cancer, starting androgen-deprivation therapy (ADT) without bone metastases. Participants must have started ADT within the last 3 months, plan to continue it for at least another 6 months, have specific levels of vitamin D and calcium in their blood, normal kidney function, and not take other calcium/vitamin D supplements.

Inclusion Criteria

I have prostate cancer stages I-IV without bone spread, but lymph nodes may be involved.

I am 60 years old or older.

I recently started or will start hormone therapy for my cancer, with at least 6 months of treatment ahead.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-dose vitamin D or placebo orally throughout the study, with blood collection and DXA scans conducted

52 weeks

Regular visits for blood collection and DXA scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• D Vitamin

Trial Overview The study tests if high-dose vitamin D can prevent bone loss caused by ADT in older prostate cancer patients. It involves taking either high-dose vitamin D or a placebo while undergoing regular assessments like bone scans and quality-of-life surveys to see if there's an improvement in bone health, reduction in falls, or less fatigue.

How Is the Trial Designed?

Group I: Arm I (HDVD) Experimental Treatment 5 Interventions

Patients receive HDVD PO QW for 52 weeks. Patients also undergo collection of blood and DXA scan on study.

Group II: Arm II (placebo) Placebo Group 5 Interventions

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

Who Is Running the Clinical Trial?

University of Rochester NCORP Research Base

Lead Sponsor

Trials

14

Recruited

9,100+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Calcitriol and its less hypercalcaemic analogues, EB1089 and CB1093, effectively inhibited the growth of prostate cancer in rodent models, suggesting their potential as therapeutic agents.

The newer analogues resulted in lower serum calcium levels compared to calcitriol, indicating they may provide a safer treatment option while still targeting the vitamin D receptor to inhibit tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D receptor-dependent antitumour effects of 1,25-dihydroxyvitamin D3 and two synthetic analogues in three in vivo models of prostate cancer. Oades, GM., Dredge, K., Kirby, RS., et al.[2019]

1,25-dihydroxycholecalciferol (1,25-D3) and its less-hypercalcemic analogue, Ro25-6760, showed significant growth inhibition of prostate cancer cells in vitro, with an IC50 of approximately 20 microM, indicating their potential as effective treatments.

In vivo studies demonstrated that both 1,25-D3 and Ro25-6760 (at a dose of 5 micrograms) reduced tumor volume and the size and number of lung metastases in a rat model of prostate cancer, suggesting their therapeutic potential in advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system. Getzenberg, RH., Light, BW., Lapco, PE., et al.[2013]

Oral vitamin D3 supplementation significantly increased levels of calcitriol and other vitamin D metabolites in prostate tissue, especially at the highest dose of 40,000 IU/d, indicating a dose-dependent effect.

While the study did not find significant differences in Ki67 expression (a marker of cell proliferation) among the different vitamin D doses, higher calcitriol levels were associated with lower Ki67 intensity, suggesting potential benefits in reducing prostate cancer cell activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and ki67 labeling in prostate cancer patients. Wagner, D., Trudel, D., Van der Kwast, T., et al.[2023]

In a study of 108 men undergoing androgen deprivation therapy (ADT) for prostate cancer, 66% had low levels of 25-OH vitamin D (<32 ng/mL), indicating a common deficiency in this patient group.

Vitamin D supplementation of 800 IU/day was effective in raising 25-OH vitamin D levels, and the study supports the recommendation for such supplementation in men receiving ADT, particularly highlighting the need for monitoring and addressing vitamin D levels in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of vitamin D levels in men receiving androgen deprivation therapy for prostate cancer. Mennen-Winchell, LJ., Grigoriev, V., Alpert, P., et al.[2015]

In a study of 120 men with recurrent prostate cancer and 50 with localized prostate cancer, vitamin D deficiency was found to be common, with 40% of men with recurrent disease and 18% of those with localized disease having levels below 20 ng/mL.

The study also revealed that factors such as metastatic disease and the season of blood sampling were linked to vitamin D deficiency, highlighting the need for monitoring vitamin D levels in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency and insufficiency among patients with prostate cancer. Trump, DL., Chadha, MK., Sunga, AY., et al.[2022]

In a study of 1822 prostate cancer patients, higher prediagnostic levels of 25(OH) vitamin D were associated with lower total mortality and a reduced risk of dying from prostate cancer, suggesting a potential link between vitamin D levels and cancer prognosis.

No significant association was found between 1,25(OH)(2)D levels and mortality, indicating that the benefits observed may be specifically related to 25(OH)D, particularly in patients diagnosed within five years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer. Fang, F., Kasperzyk, JL., Shui, I., et al.[2022]

Oral vitamin D3 supplementation significantly increased levels of calcitriol and other vitamin D metabolites in prostate tissue, especially at the highest dose of 40,000 IU/d, without adverse effects on safety measures.

While Ki67 expression, a marker of cell proliferation, did not differ significantly among the vitamin D dose groups, higher levels of calcitriol were inversely associated with Ki67 intensity, suggesting potential benefits in reducing prostate cancer cell proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary on "randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and Ki67 labeling in prostate cancer patients." Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R, Department of Nutritional Sciences, University of Toronto, Ontario, Canada.: J Clin Endocrinol Metab 2013;98(4):1498-507 [Epub 2013 Mar 5]. Olumi, AF.[2018]

Vitamin D, particularly its active form 1,25(OH)(2)D, has shown promising effects in preventing and treating prostate cancer by promoting cell differentiation and inhibiting cancer cell growth, based on its ability to act on prostate cells that have receptors for this hormone.

While vitamin D may help prevent prostate cancer, existing tumors may require treatment with 1,25(OH)(2)D or its analogs, though the risk of hypercalcemia remains a challenge that researchers are addressing through various dosing strategies in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D and intervention trials in prostate cancer: from theory to therapy. Schwartz, GG.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11214601/

High-dose vitamin D to attenuate bone loss in patients with ... HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02064946?cond=(BONE%20MINERAL%20DENSITY%20QUANTITATIVE%20TRAIT%20LOCUS)%20OR%20(LGR4)&rank=4

High-dose Vitamin D Supplementation for ADT-induced ... The purpose of this study is to test the efficacy of a high-dose vitamin D supplementation regimen in reducing androgen deprivation therapy (ADT)-related side ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2748796

Effect of High-Dose Vitamin D Supplementation on ... This randomized trial compares the effects of 400 vs 4000 vs 10 000 IU of vitamin D on total volumetric bone mineral density and bone ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1297319X2500017X

Daily or intermittent vitamin D supplementation in patients ... Other studies suggest that intermittent doses may increase the fall risk (monthly 60,000 IU vitamin D3 versus placebo), or that the risk of falls is higher with ...

5. nature.com nature.com/articles/s41574-021-00593-z

The health effects of vitamin D supplementation: evidence ... A meta-analysis suggested that vitamin D supplementation results in a modest decrease in cancer mortality. Over 60 Mendelian randomization ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8946001/

Vitamin D Metabolites in Nonmetastatic High-Risk Prostate ... We measured three vitamin D3 metabolites in 32 selected prostate cancer patients after surgery at four time points over four years. Within a large European ...

7. cancer.gov cancer.gov/about-cancer/causes-prevention/risk/diet/vitamin-d-fact-sheet

Vitamin D and Cancer - NCI The current safe upper intake level of vitamin D for adults and children older than 8 years of age is 100 μg per day (4000 IU per day).