High-Dose Vitamin D for Bone Loss in Prostate Cancer

Overseen By Olivia Tauriello

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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment High-Dose Vitamin D for Bone Loss in Prostate Cancer?

Research suggests that vitamin D, including forms like cholecalciferol (vitamin D3), may help prostate cancer patients because prostate cells can convert it into an active form that might slow cancer growth. Additionally, vitamin D has shown potential benefits in preventing prostate cancer and improving outcomes, although more research is needed to confirm its effectiveness specifically for bone loss in prostate cancer patients. ^{1 2 3 4 5}

Is high-dose vitamin D safe for humans?

High doses of vitamin D, particularly in the form of 1,25-dihydroxyvitamin D3, can lead to hypercalcemia (high calcium levels in the blood), which is a safety concern. However, strategies like pulse dosing and using less calcemic analogs have been explored to reduce this risk in clinical trials. ^{2 4 5 6 7}

How is high-dose vitamin D treatment different for prostate cancer?

High-dose vitamin D treatment for prostate cancer is unique because it leverages the ability of prostate cells to locally produce the active form of vitamin D, calcitriol, which can help slow cancer cell growth. Unlike other treatments, it focuses on enhancing the body's natural vitamin D metabolism to exert anti-cancer effects, although the risk of high calcium levels in the blood (hypercalcemia) is a concern. ^{2 4 5 7 8}

Research Team

Luke Peppone, PhD

Principal Investigator

University of Rochester NCORP Research Base

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Patients receive HDVD PO throughout the study. Patients also undergo collection of blood and DXA scan on study.

Group II: Arm II (placebo, DXA scan, blood collection, questionnaire) Placebo Group 5 Interventions

Patients receive placebo PO throughout the study. 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+

Findings from Research

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]

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]

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, 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency and insufficiency among patients with prostate cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer. [2022]

4. United States 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. [2023]

5. United States 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]. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system. [2013]

7. England 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. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Determinants of vitamin D levels in men receiving androgen deprivation therapy for prostate cancer. [2015]