Vitamin D Supplementation for Breast Cancer

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must be taking: Vitamin D

Disqualifiers: Nephrolithiasis, Sarcoidosis, High calcium, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 26 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding vitamin D supplements to standard neoadjuvant chemotherapy can improve outcomes for individuals with triple negative breast cancer. The trial consists of two parts: one group receives vitamin D supplements with their regular chemotherapy, while the other group does not. The focus is on individuals with vitamin D deficiency, as researchers believe supplements may enhance treatment response in this group. Suitable candidates for the trial include those diagnosed with triple negative breast cancer who plan to start chemotherapy soon and have low vitamin D levels. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently taking Vitamin D at a dose of 50,000 IU once weekly, you cannot participate in the study.

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

Research has shown that taking vitamin D is generally safe. Studies have found no increased risk of cancer or heart problems associated with its use. In some studies, participants took vitamin D without experiencing major side effects.

Regarding breast cancer, researchers have explored vitamin D for its potential benefits. While it may aid in fighting cancer, no evidence suggests it causes harm or serious side effects. This makes vitamin D a relatively safe option alongside standard chemotherapy treatments.

Overall, vitamin D is considered safe for most people, especially at usual supplement doses. It is important to consult a doctor before starting any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Vitamin D supplementation for breast cancer because it offers a potentially simple way to enhance the efficacy of existing chemotherapy treatments. Unlike traditional treatments that focus solely on attacking cancer cells, Vitamin D might play a role in boosting the body's overall immune response, potentially improving outcomes for patients with deficient levels. This supplementation is convenient, administered orally just once a week, making it an easy addition to the current standard of care. By exploring the role of Vitamin D in cancer treatment, researchers hope to uncover new ways to support the body’s fight against cancer with fewer side effects.

What evidence suggests that vitamin D supplementation could be an effective treatment for breast cancer?

Research has shown that vitamin D may help fight various types of cancer, including breast cancer. Some studies found that women with higher vitamin D levels had a 50% lower chance of developing breast cancer compared to those with lower levels. However, most research has not consistently proven that vitamin D supplements reduce the risk of breast cancer. In this trial, participants in the Vitamin D Supplementation Group will receive oral Vitamin D3 along with standard chemotherapy to explore its potential benefits. Meanwhile, the Observational Arm will receive standard chemotherapy without additional Vitamin D3 supplementation. This mixed evidence suggests a possible benefit, but it is not fully confirmed for breast cancer specifically. ^{1 4 6 7 8}

Who Is on the Research Team?

Emily H Douglas, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults with triple negative breast cancer who are vitamin D deficient and scheduled for surgery after chemotherapy. They must be in good enough health to participate, agree to use contraception, and have not received prior treatment for their cancer. People with a history of kidney stones, sarcoidosis, high calcium levels, allergies to vitamin D-like compounds or taking high-dose Vitamin D cannot join.

Inclusion Criteria

I am scheduled for surgery to remove breast cancer and check lymph nodes after chemotherapy.

I can take care of myself and am up and about more than half of my waking hours.

Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria

I have had kidney stones in the past year.

Pregnant women

I have had treatments like surgery or chemotherapy for my cancer before joining this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy and vitamin D supplementation

26 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Standard of Care Neoadjuvant Chemotherapy
• Vitamin D3

Trial Overview The study tests if adding Vitamin D3 supplements to standard neoadjuvant chemotherapy improves the rate at which patients achieve complete absence of cancer in the breast tissue after treatment (pathologic complete response), compared to historical rates in patients with sufficient vitamin D.

How Is the Trial Designed?

Group I: Vitamin D Supplementation Group - Deficient Levels Experimental Treatment 3 Interventions

Along with standard of care neoadjuvant chemotherapy treatments and procedures, participants will receive oral 50,000 international units of Vitamin D3 supplementation at the initiation of chemotherapy once a week.

Group II: Observational Arm - Vitamin D at Normal Levels Active Control 1 Intervention

Standard of care neoadjuvant chemotherapy

Standard of Care Neoadjuvant Chemotherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Neoadjuvant Chemotherapy for:

• Breast cancer
• Triple-negative breast cancer

Approved in United States as Neoadjuvant Chemotherapy for:

• Breast cancer
• Triple-negative breast cancer

Approved in Canada as Neoadjuvant Chemotherapy for:

• Breast cancer
• Triple-negative breast cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 144 women undergoing neoadjuvant chemotherapy for breast cancer, low serum vitamin D levels were linked to a significantly higher likelihood (2.68 times) of not achieving a pathologic complete response (pCR), indicating that vitamin D may play a role in treatment efficacy.

The research suggests that maintaining adequate vitamin D levels during chemotherapy could potentially improve breast cancer outcomes, highlighting the need for further prospective trials to explore this modifiable factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Vitamin D Levels Affect Pathologic Complete Response in Patients Undergoing Neoadjuvant Systemic Therapy for Operable Breast Cancer. Chiba, A., Raman, R., Thomas, A., et al.[2019]

In a study of 327 women undergoing neoadjuvant chemotherapy for breast cancer, vitamin D deficiency was linked to a lower likelihood of achieving a pathologic complete response (pCR), indicating that adequate vitamin D levels may enhance treatment effectiveness.

While vitamin D deficiency did not show a significant overall impact on survival rates, there was a trend suggesting that it could affect progression-free survival in specific subgroups, particularly in triple-negative and hormone receptor-positive breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of vitamin D on pathological complete response and survival following neoadjuvant chemotherapy for breast cancer: a retrospective study. Viala, M., Chiba, A., Thezenas, S., et al.[2019]

In a study of 308 patients with nonmetastatic HER2-positive breast cancer, those who received vitamin D (VD) supplementation during neoadjuvant chemotherapy showed significantly improved disease-free survival (DFS) compared to those who did not, with a hazard ratio of 0.36.

While vitamin D supplementation was linked to better DFS, there were no significant differences in overall survival (OS) based on vitamin D use or other factors, indicating that VD may specifically enhance long-term disease management rather than overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer. Zeichner, SB., Koru-Sengul, T., Shah, N., et al.[2015]

In a phase II trial involving 44 early breast cancer patients undergoing chemotherapy, high-dose oral vitamin D supplementation (100,000 IU every 3 weeks) was found to be safe and effective, with 47.7% of patients achieving normalized vitamin D levels by the end of the treatment.

While no serious vitamin D-related toxicity was reported, 29.5% of patients experienced mild hypercalciuria, leading to the temporary cessation of supplementation in some cases, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Multicenter Trial on High-Dose Vitamin D Supplementation for the Correction of Vitamin D Insufficiency in Patients with Breast Cancer Receiving Adjuvant Chemotherapy. Chartron, E., Firmin, N., Touraine, C., et al.[2022]

Vitamin D deficiency is common among breast cancer patients and is linked to various aspects of the disease, including risk factors, prognosis, and treatment interactions, highlighting the need for better management of vitamin D levels in this population.

Current recommendations for addressing vitamin D deficiency in breast cancer patients are inadequate, and further randomized clinical trials are necessary to establish effective and safe correction strategies, especially after adjuvant treatments that can worsen bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vitamin D and breast cancer: physiopathology, biological and clinical implications]. Firmin, N., Lamy, PJ., Romieu, G., et al.[2014]

In a study of 215 early breast cancer patients undergoing chemotherapy, tailored high-dose vitamin D supplementation significantly improved the normalization of vitamin D levels, with 30% achieving normal levels compared to only 12.6% in the conventional supplementation group after 6 months.

The high-dose vitamin D regimen was well tolerated, showing no significant increase in treatment-related toxicity, indicating it is a safe option for restoring vitamin D levels in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients: a randomized phase III study. Jacot, W., Firmin, N., Roca, L., et al.[2020]

A significant 74% of premenopausal women with breast cancer were found to be vitamin D deficient at the start of chemotherapy, highlighting a critical health concern in this population.

After one year of vitamin D supplementation, less than 15% of white and Hispanic women, and none of the black women, reached sufficient vitamin D levels, suggesting that current supplementation guidelines may be inadequate for improving vitamin D status in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. Crew, KD., Shane, E., Cremers, S., et al.[2022]

In a study involving 169 breast cancer patients, serum vitamin D levels significantly decreased during neoadjuvant chemotherapy, with a median drop of 16 nmol/L, indicating that chemotherapy may negatively impact vitamin D status.

Despite the decrease in vitamin D levels, there was no correlation found between baseline or post-treatment vitamin D levels and the pathological response to chemotherapy, suggesting that vitamin D may not be a reliable predictor of treatment outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01). Charehbili, A., Hamdy, NA., Smit, VT., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3267821/

Vitamin D and Breast Cancer - PMC Vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00976339

Study of Vitamin D for Premenopausal Women at High Risk ... Based upon observational data, women with serum 25(OH) D levels greater than 40-50 ng/ml had a 50% lower risk of breast cancer compared to women with vitamin D ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8049142/

Effect of Vitamin D Supplementation on Risk of Breast Cancer There is insufficient evidence to support the efficacy of vitamin D supplementation in breast cancer risk and change of mammography density.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225000085

The status of serum 25(OH)D levels is related to breast ... However, most randomized controlled trials have not demonstrated a clear reduction in breast cancer incidence following Vitamin D3 supplementation [45].

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2773074

Effect of Vitamin D3 Supplements on Development ... These findings suggest that vitamin D 3 may reduce the risk of developing advanced cancer among adults without a diagnosis of cancer at baseline.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02186015

Safety, Feasibility and Efficacy of Vitamin D ... This pilot study will evaluate the feasibility of vitamin D3 supplementation in women with MBC, providing much needed data on the preliminary safety and ...

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

Vitamin D and Cancer - NCI After 5 years of follow-up, the vitamin D/omega-3 group had the same overall cancer incidence as the placebo group (29). The incidence of breast ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809944

Vitamin D Supplements and Prevention of Cancer ... Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo.