Triple Negative Breast CancerPhase 2NCT04677816
Impact of Vitamin D Supplementation on the Rate of Pathologic Complete Response in Vitamin D Deficient Patients
A Phase 2 study testing Vitamin D3 and Drug Diary in people with Triple Negative Breast Cancer and Vitamin D Deficiency, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer, Vitamin D Deficiency, Invasive Breast Cancer
- What is being tested?
- Vitamin D3 and Drug Diary
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2021to Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women or men with histologically confirmed invasive mammary carcinoma.
- Known triple negative ER/PR/HER2 receptor status as defined by:
- ER and PR less than or equal to 10% and HER2 negative based on one of the following:
- IHC 0 or 1+
- IHC 2+ and FISH negative
- IHC 2+ and FISH equivocal and no indication for HER2 targeted therapy based on the treating investigators discretion (i.e., HER2: CEP17 ratio < 2.0 or HER2 total copy number <6)
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- Patients who plan to undergo neoadjuvant chemotherapy prior to definitive surgical management. Participants are eligible up to 2 weeks after initiating neoadjuvant chemotherapy.
- ECOG performance status of 0, 1 or 2.
- Age ≥ 18.
- The effects of high dose vitamin D on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).
Who cannot join
- Patients with nephrolithiasis within the past year.
- Patients with known sarcoidosis.
- Patients with corrected calcium >10.5 mg/dL within 30 days prior to initiation of chemotherapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vitamin D.
- Pregnant women are excluded from this study because vitamin D supplementation greater than the recommended daily allowance (RDA) is a pregnancy class C agent with no adequate or well controlled studies in humans.
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with high dose vitamin D (greater than RDA), women who are breastfeeding are excluded from this study.
- Prior treatment for this malignancy including surgery, radiation therapy, chemotherapy, hormonal therapy or investigational agent prior to study entry.
- Patients currently taking Vitamin D at a dose of 50,000 International Units (IU) once weekly.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Wake Forest Baptist Health Sciences
Winston-Salem, North Carolina, 27157
Study Coordinator, 336-716-5772, Brandy.Baker@advocatehealth.org
Emily H Douglas, MD
About this study
Official title: Impact of Vitamin D Supplementation on the Rate of Pathologic Complete Response in Vitamin D Deficient Patients Receiving Neoadjuvant Chemotherapy for Operable Triple Negative Breast Cancer
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.
Read the detailed description
Primary Objective: To determine if pathologic complete response in vitamin D deficient patients receiving vitamin D supplementation during neoadjuvant chemotherapy for operable triple negative breast cancer is greater than or equal to 60% or less than or equal to pathologic complete response in historical controls (30%) using a one-stage phase II design.
Secondary Objective(s):
- To estimate the proportion of patients with residual cancer burden (RCB) classes I, II, and III in vitamin D deficient patients receiving vitamin D supplementation during neoadjuvant chemotherapy for operable triple negative breast cancer.
- To estimate pathologic complete response reaction in the observational arm of vitamin D sufficient patients receiving neoadjuvant chemotherapy for operable triple negative breast cancer.
- To determine the feasibility of delivery of vitamin D supplementation with standard of care chemotherapy.
- To determine the safety and tolerability of the combination of vitamin D supplementation with standard of care chemotherapy.
- To estimate the change in vitamin D receptor (VDR) expression from pre- and post-neoadjuvant treatment breast tumor tissue samples of vitamin D deficient patients.
- To estimate the change in vitamin D receptor (VDR) expression from pre- to post-neoadjuvant treatment breast tumor tissue samples in a sample of 5 vitamin D sufficient patients.
- To estimate the changes in the fecal microbiome of vitamin D deficient patients from pre- to post-neoadjuvant treatment.
- To estimate the changes in the fecal microbiome in a sample of 5 vitamin D sufficient patients from pre- to post-neoadjuvant treatment.
Patients will be followed for a minimum of 30 days after the last study intervention is administered for adverse events monitoring.
Patients will be followed for 30 days after removal from study or until death, whichever occurs first. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.
- Being tested
- Standard of Care Neoadjuvant Chemotherapy (NAC), Vitamin D3, Drug Diary
- Medical subject headings
- Triple Negative Breast Neoplasms, Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of Care Neoadjuvant Chemotherapy (NAC)Drug
Participants will receive standard of care neoadjuvant chemotherapy with doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) for 4 cycles and paclitaxel (80 mg/m2) weekly for 12 cycles. Doxorubicin and cyclophosphamide (AC) may be administered on a classical every 3 week or dose dense every 2-week (with growth factor support) schedule at the treating physician's discretion. Routine incorporation of carboplatin is not required, however use of carboplatin (AUC 1.5 to 2 weekly or AUC 6 on week 1, 4, 7, and 10) with paclitaxel is allowed at the treating investigator's discretion.
Upon completion of neoadjuvant chemotherapy, all patients will undergo definitive surgery with either breast conservation or mastectomy with axillary lymph node staging. Type of surgery will be determined by the treating physician.
Vitamin D3Dietary supplement
Participants with deficient levels of vitamin D will receive vitamin D supplementation at the initiation of chemotherapy with 50,000 IU of oral vitamin D3 (cholecalciferol) once a week to be continued for 20 weeks during neoadjuvant chemotherapy.
Drug DiaryOther
Participants that will receive Vitamin D will be asked to fill out a drug diary on a daily basis. Compliance and feasibility will be assessed through a drug diary and pill counts at set time points.
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D Supplementation Group - Deficient Levels | Experimental | 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. Receives: Drug: Standard of Care Neoadjuvant Chemotherapy (NAC); Dietary Supplement: Vitamin D3; Other: Drug Diary |
| Observational Arm - Vitamin D at Normal Levels | Active comparator | Standard of care neoadjuvant chemotherapy Receives: Drug: Standard of Care Neoadjuvant Chemotherapy (NAC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Pathologic Complete Response (pCR) in Vitamin D Supplementation Group
Investigators will determine whether the proportion responding (pCR) is less than or equal to 30% or greater than or equal to 60% using a one-stage phase II design. All participants in the intervention group who are evaluable will be included in the analysis. Pathologic complete response, which is also characterized as residual cancer burden 0, is defined as a final surgical pathologic diagnosis of ypT0 ypN0 or ypTis ypN0. Only the vitamin D deficient patients will be included in the primary statistical analysis.
Measured: Up to 22 weeks
Secondary outcomes (9)
Number of Participants with Residual Cancer Burden (RCB) Index - Vitamin D Supplementation Group
Five variables are included in the calculation formula. These include: 1) Primary tumor bed area, defined as the largest two dimensions (mms) of the residual tumor bed in the breast (largest tumor bed if multicentric disease), 2) Overall cancer cellularity (as percentage of area), 3) Percentage of cancer that is in situ disease, 4) Number of positive lymph nodes and 5) Diameter of largest metastasis. The calculated residual cancer burden index will be categorized as one of four residual cancer burden classes RCB-0 (pathologic complete response), minimal residual disease (RCB-I), moderate residual disease (RCB-II), or extensive residual disease (RCB-III). Investigators will use frequencies to describe the residual cancer burden in classes I, II, and III in the women who receive the vitamin D supplementation. We will perform these analyses for all women who are evaluable.
Measured: Up to 22 weeks
Number of Participants with Residual Cancer Burden (RCB) Index - Observational Arm
Five variables are included in the calculation formula. These include: 1) Primary tumor bed area, defined as the largest two dimensions (mms) of the residual tumor bed in the breast (largest tumor bed if multicentric disease), 2) Overall cancer cellularity (as percentage of area), 3) Percentage of cancer that is in situ disease, 4) Number of positive lymph nodes and 5) Diameter of largest metastasis. The calculated residual cancer burden index will be categorized as one of four residual cancer burden classes RCB-0 (pathologic complete response), minimal residual disease (RCB-I), moderate residual disease (RCB-II), or extensive residual disease (RCB-III). Investigators will use frequencies to describe the residual cancer burden in classes I, II, and III in the women who receive the vitamin D supplementation. We will perform these analyses for all women who are evaluable.
Measured: Up to 22 weeks
Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Accrual Rate
Will be calculated as the number of women who agreed to participate divided by the number of months of recruitment. Estimates and 95% confidence intervals will be calculated for all study participants and for the subset of evaluable participants.
Measured: Up to 22 weeks
Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Participation Rate
Will be calculated as the percent of eligible participants who agreed to participate. Estimates and 95% confidence intervals will be calculated for all study participants and for the subset of evaluable participants.
Measured: Up to 22 weeks
Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Retention Rate
Will be calculated as the number of participants on whom investigators can obtain the final surgery pathology report by the number who consented to participate. Estimates and 95% confidence intervals will be calculated for all study participants and for the subset of evaluable participants.
Measured: Up to 22 weeks
Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Adherence Rate
Will be defined by the proportion of Vitamin D supplements consumed and the proportion of women who took at least 80% of pills. Estimates and 95% confidence intervals will be calculated for all study participants and for the subset of evaluable participants.
Measured: Up to 22 weeks
Number of Adverse Events
To determine safety of intervention all adverse events will be documented and analyzed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting using frequencies of events, grade and attribution.
Measured: Up to 22 weeks
Change in Vitamin D Receptor (VDR) Expression
Investigators will use a paired t-test to examine the change in Vitamin D receptor expression from pre-post neoadjuvant treatment. VDR expression will be assessed by immunohistochemistry (IHC) and documented as percentage positive cells per field.
Measured: Up to 22 weeks
Change in Fecal Microbiomes
Investigators will examine the proportion of different bacteria taxa at each time point, and will use a marginalized two-part beta regression model to account for the compositional nature of the data. A list of all the microbiologic species will be recorded, along with their relative abundance recorded as a percentage relative abundance of the total microbiome.
Measured: Up to 22 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2020
- Study start22 Oct 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Emily H Douglas, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04677816
- Sponsor's protocol ID
- IRB00074154
- Other IDs
- WFBCCC 98121, P30CA012197
- Status last verified
- Aug 2026
- First submitted
- 15 Dec 2020
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No