High-Dose Vitamin D3 for Colon Cancer

Overseen By Kimmie Ng

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Corticosteroids, Lithium, Phenytoin, others

Disqualifiers: Pregnancy, HIV, Hepatitis, others

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how high doses of vitamin D might treat colon cancer by stopping abnormal cancer cell growth and causing cell death. Participants will receive either a high dose or a standard dose of vitamin D (also known as Vitamin D3 or Cholecalciferol) before surgery. The study seeks individuals with colon cancer who have planned surgery for either a localized tumor or resectable liver metastases (cancer that has spread to the liver but can be surgically removed). As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as regular use of vitamin D supplements, chronic oral corticosteroids, and thiazide diuretics. If you are on these medications, you may need to discontinue or switch to alternatives. It's best to discuss your specific medications with the trial team.

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

Research has shown that vitamin D3 has generally been safe in past studies. People with higher vitamin D levels in their blood have demonstrated a lower risk of developing colorectal cancer, suggesting that vitamin D3 might be safe and could help reduce cancer risk.

However, this trial is in the early stages, so detailed safety information about using high doses of vitamin D3 is not yet available. Early trials like this one focus on understanding safety, and more information will emerge as the study progresses.

Overall, previous research indicates that vitamin D3 is safe, but this study is testing higher doses. It is important to discuss any concerns with the research team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for colon cancer, which typically involve surgery, chemotherapy, and radiation, high-dose Vitamin D3 offers a unique approach by potentially enhancing the body's natural defenses. Researchers are excited about its potential because Vitamin D3 may help regulate cell growth and immune function, possibly slowing cancer progression. Another distinctive feature is its oral administration, which is less invasive compared to conventional therapies. This treatment could provide a more natural and accessible option for patients, with the possibility of fewer side effects.

What evidence suggests that high-dose Vitamin D3 might be an effective treatment for colon cancer?

Studies have shown that higher levels of vitamin D in the blood are linked to a lower risk of colon cancer and improved survival rates for those with the disease. Some research has even found that the right amount of vitamin D could halve the risk of colon cancer. Reports indicate that high doses of vitamin D can aid patients with advanced colon cancer when combined with chemotherapy. In this trial, participants will receive either high-dose Vitamin D3 or a placebo. Additionally, vitamin D may enhance the body's immune response against colon tumors by boosting the activity of certain immune cells. Overall, these findings suggest that vitamin D could be a promising treatment for colon cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Kimmie Ng

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with stage I-III colon cancer or resectable liver metastases from colon cancer, who haven't had recent chemotherapy or radiation. They must be able to swallow pills, not have a history of allergic reactions to vitamin D, and should not be on certain medications like thiazide diuretics. Pregnant women and those unable to use contraception are excluded.

Inclusion Criteria

Non-pregnant and not nursing

Women of child-bearing potential must meet specific pregnancy test criteria and agree to adequate contraception

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I have had treatment before my surgery for early-stage colon cancer.

I have had cancer before, but it meets certain conditions.

History of allergic reactions to compounds similar to vitamin D

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-In Phase

The first 6-12 participants receive high-dose vitamin D prior to surgery to analyze research samples

14-28 days

Randomized Phase

Participants are randomized to receive either high-dose or standard-dose vitamin D prior to surgery

14-28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood sample collection for follow-up 25(OH)D, calcium, and albumin determination

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Vitamin D3

Trial Overview The study tests high-dose versus standard-dose vitamin D given before surgery for colon cancer. It aims to understand how vitamin D affects the growth and death of cancer cells by interacting with the vitamin D receptor in these cells.

How Is the Trial Designed?

Group I: Vitamin D3 - Blinded Registration Experimental Treatment 1 Intervention

One capsule of vitamin D3 10,000 IU orally once daily for 14 days until the date of surgery. To allow for some flexibility in the scheduling of surgery, patients can be treated with preoperative vitamin D3 for up to 28 days. On the morning of surgery, prior to operating, a second blood sample will be collected for follow-up 25(OH)D, calcium, and albumin determination. Colon and liver resection will occur per institutional standards of care, and malignant and adjacent benign tissue will be collected for the laboratory endpoints described in this protocol.

Group II: Placebo - Blinded Registration Placebo Group 1 Intervention

One placebo capsule orally once daily for 14 days until the date of surgery. To allow for some flexibility in the scheduling of surgery, patients can be treated with preoperative placebo for up to 28 days. On the morning of surgery, prior to operating, a second blood sample will be collected for follow-up 25(OH)D, calcium, and albumin determination. Colon and liver resection will occur per institutional standards of care, and malignant and adjacent benign tissue will be collected for the laboratory endpoints described in this protocol.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Pharmavite LLC

Industry Sponsor

Trials

12

Recruited

27,200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Calcitriol, the active form of vitamin D, plays a crucial role in bone health and has been shown to significantly lower the incidence of colorectal cancer by up to 50%, based on its regulation of calcium and phosphate metabolism.

Vitamin D3 supplementation not only reduces the recurrence of polyps but also improves overall survival rates in colon cancer patients, likely by modulating the Wnt signaling pathway and inhibiting inflammation in the intestinal epithelium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D and colon cancer. Klampfer, L.[2020]

Higher levels of serum 25-hydroxyvitamin D (25(OH)D) were associated with significantly reduced mortality in colorectal cancer patients, with a hazard ratio of 0.71 for overall mortality and 0.65 for disease-specific mortality, based on a meta-analysis of 2330 patients.

Similarly, breast cancer patients with higher 25(OH)D levels showed a reduced risk of mortality, with hazard ratios of 0.62 for overall mortality and 0.58 for disease-specific mortality, based on 4413 patients, suggesting a potential benefit of maintaining adequate vitamin D levels in cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: systematic review and meta-analysis of prospective cohort studies. Maalmi, H., Ordóñez-Mena, JM., Schöttker, B., et al.[2022]

Vitamin D deficiency significantly accelerates colon tumor growth, with tumors in vitamin D deficient mice being 56% larger than those in vitamin D sufficient mice by day 18 of the study.

Novel vitamin D analogs, specifically the Gemini compounds, showed promising results in reducing tumor volume, with one analog reducing tumor size by 52% at a lower dose compared to the control group, indicating potential for new colon cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colon cancer and solar ultraviolet B radiation and prevention and treatment of colon cancer in mice with vitamin D and its Gemini analogs. Spina, C., Tangpricha, V., Yao, M., et al.[2013]

Vitamin D receptor activation may help prevent cancer at various stages, and there is evidence suggesting that higher vitamin D levels are linked to lower cancer incidence and mortality, based on both experimental and epidemiological studies.

Current randomized controlled trials (RCTs) on vitamin D and cancer may not have effectively addressed key questions, highlighting the need for new trials to determine the optimal dosage and to account for factors like baseline vitamin D levels and compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation and cancer: review of randomized controlled trials. Lazzeroni, M., Serrano, D., Pilz, S., et al.[2013]

In a study of 72 patients with metastatic colorectal cancer (mCRC), nearly all participants were found to be vitamin D insufficient, highlighting a common deficiency in this patient group.

Supplementing with 2,000 IU of cholecalciferol (vitamin D) daily for 2 years alongside standard chemotherapy did not result in any significant improvement in overall survival or progression-free survival for mCRC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D Supplementation and Survival in Metastatic Colorectal Cancer. Antunac Golubić, Z., Baršić, I., Librenjak, N., et al.[2019]

Higher serum levels of 25-hydroxyvitamin D (25(OH)D) at the time of colorectal cancer diagnosis are linked to significantly lower mortality rates, with patients in the highest quintile experiencing 37% lower mortality compared to those in the lowest quintile.

The study suggests that maintaining serum 25(OH)D levels within a normal range (30-80 ng/ml) could be beneficial for colorectal cancer patients, highlighting the importance of regular monitoring and potential supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could vitamin D sufficiency improve the survival of colorectal cancer patients? Mohr, SB., Gorham, ED., Kim, J., et al.[2015]

In a study of 1016 patients with stage III colon cancer, those with the highest predicted levels of 25-hydroxyvitamin D3 (25(OH)D) had a 38% lower risk of cancer recurrence or mortality compared to those with the lowest levels, indicating a potential protective effect of vitamin D on cancer outcomes.

Higher predicted 25(OH)D levels were linked to significantly better recurrence-free survival and overall survival, suggesting that vitamin D status may play an important role in the prognosis of colon cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance). Fuchs, MA., Yuan, C., Sato, K., et al.[2022]

In a study of 588 colorectal cancer patients, lower levels of 25-hydroxyvitamin D (25(OH)D) were linked to a significantly higher overall mortality rate, with a hazard ratio of 2.06 for those with deficient levels compared to sufficient levels.

However, the study found no significant association between 25(OH)D levels and colorectal cancer-specific mortality, indicating that while vitamin D levels may impact overall survival, they do not appear to influence the mortality directly related to colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediagnostic Vitamin D Status and Colorectal Cancer Survival by Vitamin D Binding Protein Isoforms in US Cohorts. Kim, H., Yuan, C., Nguyen, LH., et al.[2023]

In a study of 1,598 patients with stage I to III colorectal cancer, higher plasma levels of 25-hydroxyvitamin D (25-OHD) were linked to significantly better survival outcomes, particularly in stage II patients, suggesting that vitamin D may play a protective role in cancer prognosis.

The research also found interactions between vitamin D levels and specific genetic variations in the vitamin D receptor (VDR), indicating that both vitamin D status and genetic factors may influence survival in colorectal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. Zgaga, L., Theodoratou, E., Farrington, SM., et al.[2022]

The active form of vitamin D, 1α,25-dihydroxyvitamin D(3), plays a crucial role in regulating various biological processes and has been linked to a reduced risk of colorectal cancer, as it influences gene expression and inhibits cancer cell proliferation.

Current evidence suggests that vitamin D may have protective effects against colon cancer, but more extensive and well-designed clinical trials are needed to fully understand its potential in prevention and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D and colon cancer. Pereira, F., Larriba, MJ., Muñoz, A.[2022]

A noncalcemic synthetic analogue of vitamin D significantly reduced total tumor load in Apc(min) mice by 36%, while the active form of vitamin D (1alpha,25-(OH)(2)-D(3)) showed a 46% decrease, indicating potential for chemoprevention in colon cancer.

The analogue did not elevate serum calcium levels significantly, suggesting it may be a safer option compared to traditional vitamin D treatments, which caused notable increases in calcium and reduced food intake and growth rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse. Huerta, S., Irwin, RW., Heber, D., et al.[2013]

A recent Phase 2 trial of vitamin D3 supplementation in patients with metastatic colorectal cancer showed promising results, suggesting potential anti-cancer activities of vitamin D.

A Phase 3 trial is currently underway to further investigate the efficacy of vitamin D in treating colorectal cancer, building on the encouraging findings from the earlier trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation: a potential therapeutic agent for metastatic colorectal cancer. Yuan, C., Ng, K.[2023]

This updated meta-analysis of 11 studies involving 7718 colorectal cancer patients shows that higher blood levels of 25-hydroxyvitamin D (25(OH)D) are associated with improved overall and colorectal cancer-specific survival, with hazard ratios of 0.68 and 0.67, respectively.

The strongest associations were found in studies from Europe with larger sample sizes and patients at various cancer stages, suggesting that vitamin D supplementation could potentially enhance the prognosis for colorectal cancer patients and warrants further investigation through randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Blood 25-Hydroxyvitamin D Levels and Survival in Colorectal Cancer Patients: An Updated Systematic Review and Meta-Analysis. Maalmi, H., Walter, V., Jansen, L., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9537583/

Vitamin D and Colorectal Cancer: Current Perspectives and ... Previous studies show that higher circulating 25(OH)D levels are associated with reduced risk of colorectal cancer (CRC) and improved survival.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2808574

The Death D-Fying Vitamin D3 for Digestive Tract Cancers ... A quantitative meta-analysis on optimal vitamin D status for colorectal cancer prevention reported a 50% risk reduction associated with a serum ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4922494/

Vitamin D and Physical Activity in Patients with Colorectal ... Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. J Clin Oncol. 2014;32(23):2430–2439. doi: 10.1200/JCO ...

4. dana-farber.org dana-farber.org/newsroom/news-releases/2019/high-dose-vitamin-d-shows-benefit-in-patients-with-advanced-colorectal-cancer

High-dose vitamin D shows benefit in patients with ... Results of a small clinical trial suggest that supplementing chemotherapy with high doses of vitamin D may benefit patients with metastatic colorectal cancer.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3607

Impact of vitamin d on the colon tumor immune ... Additionally, vitamin D supplementation led to greater co-localization between CD3+CD8+ T cells and tumor cells (p< 0.001) compared to placebo.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8201292/

Vitamin D Intake and the Risk of Colorectal Cancer The present meta-analysis demonstrates that high dietary vitamin D is associated to CRC prevention. However, larger and high-quality prospective ...

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

Vitamin D and Cancer - NCI Higher vitamin D levels have been consistently associated with reduced risks of colorectal cancer (12) and, to a lesser extent, bladder cancer ( ...

8. gastrojournal.org gastrojournal.org/article/S0016-5085(21)03235-2/fulltext

Total Vitamin D Intake and Risks of Early-Onset Colorectal ... In conclusion, we found evidence that higher total vitamin D intake is associated with decreased risks of early-onset CRC and precursors. Our ...