Clinical trial NCT04677816: Impact of Vitamin D Supplementation on the Rate of Pathologic Complete Response in Vitamin D Deficient Patients
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Vitamin D Deficiency
Invasive Breast Cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-12-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 are scheduled to undergo definitive surgical treatment with lumpectomy or mastectomy with axillary lymph node staging after 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.

Primary outcomes:
measure: Number of Pathologic Complete Response (pCR) in Vitamin D Supplementation Group
timeFrame: Up to 26 months
Secondary outcomes:
measure: Number of Participants with Residual Cancer Burden (RCB) Index - Vitamin D Supplementation Group
timeFrame: Up to 26 months
measure: Number of Participants with Residual Cancer Burden (RCB) Index - Observational Arm
timeFrame: Up to 26 months
measure: Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Accrual Rate
timeFrame: Up to 26 months
measure: Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Participation Rate
timeFrame: Up to 26 months
measure: Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Retention Rate
timeFrame: Up to 26 months
measure: Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Adherence Rate
timeFrame: Up to 26 months
measure: Number of Adverse Events
timeFrame: Up to 26 months
measure: Change in Vitamin D Receptor (VDR) Expression
timeFrame: Up to 26 months
measure: Change in Fecal Microbiomes
timeFrame: Up to 26 months
measure: Change in Mammary Gland Microbiomes
timeFrame: Up to 26 months
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Emily H Douglas, MD
role: PRINCIPAL_INVESTIGATOR
References: