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

NCT ID: NCT04677816

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-22
• Study Completion Date: 2026-03-31

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.

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 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 and mammary gland microbiome of vitamin D deficient patients from pre- to post-neoadjuvant treatment, and to explore the concordance in the changes between the mammary and fecal microbiome.
• To estimate the changes in the fecal microbiome and mammary gland 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vitamin D Supplementation Group - Deficient Levels

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 Type: EXPERIMENTAL

Standard of Care Neoadjuvant Chemotherapy (NAC)

Intervention Type: 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 D3

Intervention Type: 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.

Drug Diary

Intervention Type: 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.

Observational Arm - Vitamin D at Normal Levels

Standard of care neoadjuvant chemotherapy

Group Type: ACTIVE_COMPARATOR

Standard of Care Neoadjuvant Chemotherapy (NAC)

Intervention Type: 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.

Interventions

Standard of Care Neoadjuvant Chemotherapy (NAC)

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.

Intervention Type: DRUG

Vitamin D3

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.

Intervention Type: DIETARY_SUPPLEMENT

Drug Diary

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily H Douglas, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest Baptist Health Sciences

Winston-Salem, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Study Coordinator

Role: CONTACT

jwyche@wakehealth.edu

336-713-0031

Facility Contacts

Study Nurse

Role: primary

Other Identifiers

WFBCCC 98121

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00074154

Identifier Type: -

Identifier Source: org_study_id