Vitamin D for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Gerardo Colon-Otero

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Mayo Clinic

Must not be taking: Vitamin D, Multivitamins

Disqualifiers: Hypersensitivity to vitamin D, Dialysis, Cirrhosis, Hypercalcemia, others

No Placebo Group

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This early phase I is to find out how common vitamin D insufficiency is among African American patients with a history of prostate cancer that has not spread to other parts of the body (localized) or has spread to other places in the body (metastatic) and how vitamin D insufficiency affects the immune system. This study also aims to find out if replacing vitamin D results in normalization of the immune function. Information from this study may benefit prostate cancer patients by identifying vitamin D insufficiency which in several studies had been found to contribute to more aggressive prostate cancers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've been taking a vitamin D or multivitamin supplement with more than 400 IU of vitamin D daily for the past month.

What data supports the effectiveness of the drug Cholecalciferol (Vitamin D3) for prostate cancer?

Research suggests that Vitamin D3 might help prostate cancer patients because it can be converted into an active form that affects cancer cells. Some studies show that Vitamin D supplementation may lower prostate-specific antigen (PSA) levels, which are markers of prostate cancer activity, and could improve survival when used with standard treatments. ^{1 2 3 4 5}

Is Vitamin D (Cholecalciferol) safe for use in humans?

In a study where patients were given 2,000 IU of Vitamin D (Cholecalciferol) daily, no side effects were reported, suggesting it is generally safe at this dosage. ^{4 5 6 7 8}

How does the drug Vitamin D3 differ from other treatments for prostate cancer?

Vitamin D3 is unique because it can be locally converted by prostate cells into an active form called calcitriol, which may help slow cancer cell growth and promote cell maturation, unlike traditional treatments that do not utilize this pathway. ^{4 5 9 10 11}

Research Team

Gerardo Colon-Otero

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for African American males aged 18 or older with a history of localized or metastatic prostate cancer and low vitamin D levels. They must be willing to visit the Mayo Clinic for blood collection at the start and after 8 weeks. Those with hypercalcemia, end-stage renal failure, current high-dose vitamin D intake, recent chemotherapy/surgery/radiation, hypersensitivity to vitamin D, liver cirrhosis, or legal/medical issues affecting consent are excluded.

Inclusion Criteria

I have had prostate cancer before, whether it was localized, spread, or came back.

I am an African American male aged 18 or older.

Patients with Vitamin D levels below 30 ng/mL

Exclusion Criteria

I have been taking vitamin D or a multivitamin with over 400 IU of vitamin D daily for the last month.

I am on dialysis for end-stage kidney failure.

I have liver cirrhosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants with low vitamin D3 levels receive cholecalciferol orally daily for 8 weeks. Blood samples are collected throughout the study.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on progression free survival and immune response.

Up to 2 years

Treatment Details

Interventions

• Cholecalciferol (Vitamin D Replacement)

Trial Overview The study investigates how common vitamin D insufficiency is among Black/African American prostate cancer patients and its effect on immune function. It also examines whether supplementing with cholecalciferol (vitamin D) normalizes immune responses. Participants will undergo quality-of-life assessments as part of the study.

Participant Groups

Group I: Treatment (cholecalciferol) Experimental Treatment 3 Interventions

Patients with low vitamin D3 levels receive cholecalciferol PO daily for 8 weeks in the absence of unacceptable toxicity. Patients undergo blood sample collection throughout the study.

Cholecalciferol is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Japan as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in China as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Switzerland as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a study of 26 patients with asymptomatic, PSA-progressive prostate cancer, vitamin D therapy was found to be effective, with 20% of patients showing a significant reduction in PSA levels by an average of 45.3% after 3 months.

The treatment was well tolerated, with no adverse effects on serum calcium levels, and some patients experienced stabilization of PSA levels for up to 36 months, indicating its potential as a valuable addition to prostate cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promiscuous receptor. Newsom-Davis, TE., Kenny, LM., Ngan, S., et al.[2009]

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]

Vitamin D supplementation, particularly with calcitriol at doses of 250-1000 mg for 3-8 weeks or 45 mg for 18.3 months, may help reduce prostate-specific antigen (PSA) levels and improve survival in prostate cancer patients, based on a review of 8 high-quality randomized controlled trials.

While some studies showed positive effects on PSA and survival, many others reported no significant impact, indicating that more research is needed to fully understand the role of vitamin D in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Vitamin D Supplementation in Prostate Cancer: A Systematic Review of Randomized Control Trials. Petrou, S., Mamais, I., Lavranos, G., et al.[2019]

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]

In a study of 15 patients with rising PSA levels after local prostate cancer treatments, daily administration of 2,000 IU of cholecalciferol (vitamin D) led to decreased or stable PSA levels in 9 patients for up to 21 months.

Cholecalciferol significantly prolonged the median PSA doubling time from 14.3 months to 25 months, with no reported side effects, suggesting it may be a safe and effective option for managing PSA levels in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study: potential role of vitamin D (Cholecalciferol) in patients with PSA relapse after definitive therapy. Woo, TC., Choo, R., Jamieson, M., et al.[2013]

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]

Vitamin D receptors (VDR) are present in various human prostate cancer cell lines and primary cultures, indicating that vitamin D may play a role in prostate cancer biology.

The active form of vitamin D, 1,25-D, has been shown to inhibit cell growth and stimulate PSA production in prostate cells, suggesting its potential as a therapeutic agent for chemoprevention and differentiation therapy in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D and prostate cancer. Feldman, D., Skowronski, RJ., Peehl, DM.[2019]

Vitamin D signaling is biologically active and may play a significant role in the development and prognosis of prostate cancer, suggesting it could be a target for prevention and treatment.

Current clinical data supporting the use of vitamin D compounds in prostate cancer management is limited, highlighting the need for large-scale clinical trials to explore their efficacy based on promising preclinical findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D in prostate cancer. Trump, DL., Aragon-Ching, JB.[2019]

The active form of vitamin D, 1,25(OH)2D, significantly alters gene expression in non-tumorigenic prostate cells, with thousands of transcripts changing in response to treatment, indicating its potential role in prostate cancer prevention.

Vitamin D appears to suppress key cancer-related signaling pathways (like WNT and NF-kB) and pro-inflammatory responses, while promoting protective mechanisms against oxidative stress, suggesting a multifaceted approach to limiting prostate cancer development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1. Kovalenko, PL., Zhang, Z., Cui, M., et al.[2022]

References

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

The promiscuous receptor. [2009]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Vitamin D Supplementation in Prostate Cancer: A Systematic Review of Randomized Control Trials. [2019]

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

Pilot study: potential role of vitamin D (Cholecalciferol) in patients with PSA relapse after definitive therapy. [2013]

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

Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in Nkx3.1;Pten mutant mice. [2016]

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

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

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

Vitamin D and prostate cancer. [2019]

10. China pubmed.ncbi.nlm.nih.gov

Vitamin D in prostate cancer. [2019]

11. England pubmed.ncbi.nlm.nih.gov

1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1. [2022]