High-Dose Vitamin D3 for Colon Cancer

Overseen by Kimmie Ng

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Dana-Farber Cancer Institute

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

Disqualifiers: Pregnancy, HIV, Hepatitis, others

Trial Summary

What is the purpose of this trial?

This study seeks to learn more about the vitamin D receptor and its relationship to colon cancer. The Vitamin D receptor is found in colon cancer cells. When Vitamin D binds to the receptor in the cancer cells, it may stop cancer cells from growing abnormally and may cause cancer cell death. Vitamin D has been used in other research studies and information from those other research studies suggests that Vitamin D may help in the treatment of colon cancer. Participants will receive either high-dose vitamin D or standard-dose vitamin D. The study drug will be given 14-28 days prior to your surgery. The number of days will depend on when the surgery is scheduled.

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.

What data supports the effectiveness of the drug Vitamin D3 for colon cancer?

Research shows that higher levels of vitamin D in the blood are linked to better survival rates in people with colorectal cancer. This suggests that vitamin D3 might help improve outcomes for these patients. ^{1 2 3 4 5}

Is high-dose Vitamin D3 safe for humans?

Vitamin D3, also known as cholecalciferol, is generally considered safe for humans and is important for bone health and regulating calcium levels. Some studies suggest it may also help reduce the risk of colorectal cancer and improve survival rates, but more research is needed to confirm these benefits. ^{6 7 8 9 10}

How does high-dose Vitamin D3 treatment differ from other colon cancer treatments?

High-dose Vitamin D3 treatment is unique because it involves using a high dose of the active form of vitamin D to regulate genes that control cancer cell growth and survival, potentially reducing tumor size and progression. Unlike traditional chemotherapy, it works by modulating the body's natural processes, such as calcium metabolism and inflammation, to prevent and treat colon cancer. ^{8 10 11 12 13}

Research Team

Kimmie Ng

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Other)
• Vitamin D3 (Vitamin Supplement)

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.

Participant Groups

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+

Dr. Benjamin L. Ebert

Dana-Farber Cancer Institute

Chief Executive Officer

MD from Harvard Medical School, PhD from Oxford University

Dr. Craig A. Bunnell

Dana-Farber Cancer Institute

Chief Medical Officer since 2012

MD from Harvard Medical School, MPH from Harvard School of Public Health, MBA from MIT Sloan School of Management

Pharmavite LLC

Industry Sponsor

Trials

12

Recruited

27,200+

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 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]

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]

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]

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 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]

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]

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]

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]

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]

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]

References

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

Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Could vitamin D sufficiency improve the survival of colorectal cancer patients? [2015]

3. England 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. [2022]

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

Prediagnostic Vitamin D Status and Colorectal Cancer Survival by Vitamin D Binding Protein Isoforms in US Cohorts. [2023]

5. Switzerland 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. [2018]

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

Vitamin D Supplementation and Survival in Metastatic Colorectal Cancer. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance). [2022]

8. China pubmed.ncbi.nlm.nih.gov

Vitamin D and colon cancer. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation: a potential therapeutic agent for metastatic colorectal cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Vitamin D and colon cancer. [2022]

11. England 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. [2013]

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

1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse. [2013]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation and cancer: review of randomized controlled trials. [2013]