Clinical Trials /

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

NCT04677816

Description:

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.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: IRB00070680
  • SECONDARY ID: WFBCCC 02120
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT04677816

Conditions

  • Triple Negative Breast Cancer
  • Vitamin D Deficiency

Interventions

DrugSynonymsArms
Standard of Care Neoadjuvant ChemotherapyObservational Arm - Vitamin D at Normal Levels

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Vitamin D Supplementation Group - Deficient LevelsExperimentalAlong 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.
  • Standard of Care Neoadjuvant Chemotherapy
Observational Arm - Vitamin D at Normal LevelsActive ComparatorStandard of care neoadjuvant chemotherapy
  • Standard of Care Neoadjuvant Chemotherapy

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 < 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of Pathologic Complete Response (pCR) in Vitamin D Supplementation Group
Time Frame:Up to 4 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Proportion of Participants with Residual Cancer Burden (RCB) Index - Vitamin D Supplementation Group
Time Frame:Up to 12 weeks
Safety Issue:
Description: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).
Measure:Proportion of Participants with Residual Cancer Burden (RCB) Index - Observational Arm
Time Frame:Up to 12 weeks
Safety Issue:
Description: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).
Measure:Accrual Rate
Time Frame:Up to 12 weeks
Safety Issue:
Description: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.
Measure:Participation Rate
Time Frame:Up to 12 weeks
Safety Issue:
Description: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.
Measure:Retention Rate
Time Frame:Up to 12 weeks
Safety Issue:
Description: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.
Measure:Adherence Rate
Time Frame:Up to 12 weeks
Safety Issue:
Description: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.
Measure:Number of Adverse Events
Time Frame:Up to 30 days after last day of study intervention
Safety Issue:
Description: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.
Measure:Change in Vitamin D Receptor (VDR) Expression
Time Frame:At baseline and up to 30 days after surgery
Safety Issue:
Description:Investigators will use a paired t-test to examine the change in Vitamin D receptor expression from pre-post neoadjuvant treatment.
Measure:Change in Fecal and Mammary Gland Microbiomes
Time Frame:At baseline and up to 30 days after surgery
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Wake Forest University Health Sciences

Last Updated

December 22, 2020