Impact of Vitamin D Supplementation on the Rate of Pathologic Complete Response in Vitamin D Deficient Patients

NCT04677816 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: IRB00074154WFBCCC 98121P30CA012197
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Triple Negative Breast Cancer; Vitamin D Deficiency; Invasive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 22 weeks

Secondary Outcomes (9)

• Number of Participants with Residual Cancer Burden (RCB) Index - Vitamin D Supplementation Group

  Up to 22 weeks

• Number of Participants with Residual Cancer Burden (RCB) Index - Observational Arm

  Up to 22 weeks

• Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Accrual Rate

  Up to 22 weeks

• Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Participation Rate

  Up to 22 weeks

• Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Retention Rate

  Up to 22 weeks

Study Arms (2)

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.

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

Drug: Standard of Care Neoadjuvant Chemotherapy (NAC)

Interventions

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.

Observational Arm - Vitamin D at Normal Levels; Vitamin D Supplementation Group - Deficient Levels

Vitamin D3 DIETARY_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.

Vitamin D Supplementation Group - Deficient Levels

Drug Diary OTHER

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.

Vitamin D Supplementation Group - Deficient Levels

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest Baptist Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Vitamin D Deficiency

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Emily H Douglas, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

336-713-0031; jwyche@wakehealth.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 21, 2020
• Study Start: October 22, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)