Impact of Vitamin D Supplementation on the Rate of Pathologic Complete Response in Vitamin D Deficient Patients
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorWake Forest University Health Sciences
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Women or men with histologically confirmed invasive mammary carcinoma.
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)
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Standard of Care Neoadjuvant Chemotherapy (NAC)
DrugParticipants 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
Dietary supplementParticipants 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 interventionParticipants 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.
Treatment groups
50 Participants
are divided into 2 treatment groupsGroup A: Vitamin D Supplementation Group - Deficient LevelsExperimental treatment 3 interventions
Group B: Observational Arm - Vitamin D at Normal LevelsActive comparator 1 intervention
Trial outcomes
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.
Time frame
Up to 22 weeksSecondary outcomes
1
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.
Time frame
Up to 22 weeks2
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.
Time frame
Up to 22 weeks3
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.
Time frame
Up to 22 weeks4
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.
Time frame
Up to 22 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Wake Forest University Health Sciences
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov