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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Number of Pathologic Complete Response (pCR) in Vitamin D Supplementation Group
研究概览
简要总结
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.
详细描述
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 vitamin D receptor (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 of vitamin D deficient patients from pre- to post-neoadjuvant treatment.
- To estimate the changes in the fecal 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Standard of Care Neoadjuvant Chemotherapy (NAC) (Drug)
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.
干预措施: Drug Diary (Other)
Observational Arm - Vitamin D at Normal Levels
Standard of care neoadjuvant chemotherapy
干预措施: Standard of Care Neoadjuvant Chemotherapy (NAC) (Drug)
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.
干预措施: Vitamin D3 (Dietary Supplement)
结局指标
主要结局
Number of Pathologic Complete Response (pCR) in Vitamin D Supplementation Group
时间窗: Up to 22 weeks
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.
次要结局
- Number of Participants with Residual Cancer Burden (RCB) Index - Observational Arm(Up to 22 weeks)
- Number of Participants with Residual Cancer Burden (RCB) Index - Vitamin D Supplementation Group(Up to 22 weeks)
- Number of Participants with Residual Cancer Burden (RCB) Index - Observational Arm(Up to 9 months)
- Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Accrual Rate(Up to 22 weeks)
- Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Participation Rate(Up to 22 weeks)
- Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Retention Rate(Up to 22 weeks)
- Feasibility of Delivery of Standard NAC and Vitamin D Supplementation - Adherence Rate(Up to 22 weeks)
- Number of Adverse Events(Up to 22 weeks)
- Change in Vitamin D Receptor (VDR) Expression(Up to 22 weeks)
- Change in Fecal Microbiomes(Up to 22 weeks)