Vitamin D Supplementation for Breast Cancer

Overseen By Study Nurse

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

Trial Summary

What is the purpose of this trial?

A two arm pilot study investigating the rate of pathologic complete response in patients with vitamin D deficiency and triple negative breast cancer undergoing standard neoadjuvant chemotherapy + vitamin D supplementation, including an observational arm to describe response in patients who are not deficient. Investigators hypothesize that vitamin D supplementation during neoadjuvant chemotherapy in operable triple negative breast cancer patients with vitamin D deficiency, will increase the rate of pathologic complete response chain reaction to that of vitamin D sufficient patients based on historical controls.

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.

What data supports the effectiveness of the drug Vitamin D3 in combination with chemotherapy for breast cancer?

Research suggests that higher vitamin D levels may improve the effectiveness of chemotherapy in breast cancer patients, as vitamin D can enhance the cancer-killing effects of chemotherapy. Studies have shown that patients with adequate vitamin D levels are more likely to achieve a complete response to treatment, meaning no signs of cancer are found after therapy. ^{1 2 3 4 5}

Is vitamin D supplementation safe for breast cancer patients undergoing chemotherapy?

High-dose vitamin D supplementation appears to be safe for breast cancer patients receiving chemotherapy, with no reported clinical toxicity. However, some patients experienced mild, symptom-free increases in calcium levels, which were managed by adjusting the vitamin D dosage. ^{1 2 3 5 6}

How does vitamin D supplementation differ from other treatments for breast cancer?

Vitamin D supplementation is unique because it may enhance the effectiveness of standard chemotherapy by improving the body's response to treatment and potentially increasing survival rates. Unlike other treatments, it specifically targets vitamin D deficiency, which is common in breast cancer patients and can affect treatment outcomes. ^{1 2 3 7 8}

Research Team

Emily H Douglas, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

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

Serum Vitamin D Levels Affect Pathologic Complete Response in Patients Undergoing Neoadjuvant Systemic Therapy for Operable Breast Cancer. [2019]

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

Impact of vitamin D on pathological complete response and survival following neoadjuvant chemotherapy for breast cancer: a retrospective study. [2019]

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

Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer. [2015]

4. Netherlands 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). [2022]

5. England 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. [2020]

6. Switzerland 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. [2022]

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

High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Vitamin D and breast cancer: physiopathology, biological and clinical implications]. [2014]