Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| WFBCCC 98121 | Other Identifier | Wake Forest Baptist Comprehensive Cancer Center | |
| P30CA012197 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
Not provided
Not provided
Not provided
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.
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):
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Observational Arm - Vitamin D at Normal Levels | Active Comparator | Standard of care neoadjuvant chemotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Women or men with histologically confirmed invasive mammary carcinoma.
Known triple negative ER/PR/HER2 receptor status as defined by:
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:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Study Coordinator | Contact | 336-713-0031 | jwyche@wakehealth.edu |
| Name | Affiliation | Role |
|---|---|---|
| Emily H Douglas, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest Baptist Health Sciences | Recruiting | Winston-Salem | North Carolina | 27157 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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. |
|
| 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. |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Up to 22 weeks |
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| D014808 | Vitamin D Deficiency |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
Not provided
Not provided