Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma in Basal Cell Nevus Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 2
- 主要终点
- BCC: Rate of tumor clearance
研究概览
简要总结
The purpose of this study is to study 50 patients with multiple Basal Cell Carcinoma (BCC) who will be receiving Photodynamic Therapy (PDT) as treatment for their tumors. This study wants to establish the optimal conditions for treating BCC tumors with PDT. Previous research suggests that taking Vitamin D prior to the start of PDT could help improve the effectiveness of the treatment in eliminating the BCC. Overall, this study will help establish oral Vitamin D3/PDT as a new combination therapy for skin cancer (BCC).
Photodynamic Therapy (PDT) is an investigational (experimental) technique that works by combining a photosensitizing topical agent and an intense light source to kill tumor cells. PDT is currently approved for the treatment of BCC in Europe, Canada, and Australia. However, it is experimental in the United States because it is not approved by the Food and Drug Administration (FDA).
详细描述
The overall hypothesis is that PDT could provide exceptional benefit in patients with Basal Cell Nevus Syndrome (BCNS) and multiple BCC tumors because PDT is nonmutagenic, nonscarring, and can be safely repeated many times. The specific study hypothesis is that Vitamin D might be useful as a neoadjuvant to improve tumor responses to PDT. In preclinical studies, the investigators showed that epithelial tumors are more responsive to aminolevulinic acid (ALA)-based PDT when "primed" by pre-exposure to the dietary form of Vitamin D (cholecalciferol, D3). This study will test the hypothesis that oral D3 supplements, administered over a relatively short time, can boost the effectiveness of PDT for cutaneous (BCC) in this patient population. Patients with BCNS and multiple BCC, or normal patients with at least 3 BCC tumors, will be enrolled. They will receive three PDT treatments, at two-month intervals, over a 6 month period.
Primary Objective
• To determine tumor clinical clearance rates after neoadjuvant D3/PDT, and after PDT alone. To accomplish this, the first two PDT treatments in each study patient will be randomized, i.e. one PDT session will be performed after D3 pretreatment, the other without any pretreatment.
Secondary Objective(s)
- To assess the level of PpIX accumulation in BCC lesions at various treatment visits, in the absence or presence of neoadjuvant D3. (Fluorescence dosimetry measurements)
- To assess tolerability of the technique. (Pain scale measurements)
- To assess patient satisfaction with the technique. (Cosmetic result, and questionnaire)
- To assess D3 serum levels (in serum) and VDR status (in leukocyte DNA), and correlate these results to clinical outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Neither the participant nor the treating physicians will know which patients receive the Vitamin D3 or placebo pills. Using a "coin toss" approach, the Research Pharmacist will assign each patient to a study group
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Basal Cell Nevus Syndrome (BCNS) as defined in the Consensus Statement from the first International colloquium on BCNS.
- •Major Criteria are:
- •(1) BCC prior to age 20 years, or excessive number of BCCs out of proportion to prior sun exposure and skin type;
- •(2) keratocyst of the jaw prior to age 20;
- •(3) palmar or plantar pitting;
- •(4) lamellar calcification of the falx cerebri;
- •(5) medulloblastoma;
- •(6) first degree relative with BCNS;
- •(7) Patched-1 (PTCH1) gene mutation.
- •Minor Criteria are:
- •(1) rib anomalies, or other specific skeletal malformations including kyphoscoliosis and short 4th metacarpals;
- •(2) macrocephaly;
- •(3) cleft/lip or palate;
- •(4) fibroma of the heart or ovary;
- •(5) ocular abnormalities;
- •For diagnosis of BCNS, the participant must have either 2 major criteria, one major and two minor criteria.
- •At least three BCC tumors, two of which are biopsy-proven
- •Female subjects must not become pregnant during the study
- •Subjects must be able to understand and willing to sign a written informed consent document
排除标准
- •Pregnant or nursing.
- •At risk for hypercalcemia (renal disease, sarcoidosis, etc.)
- •Taking vismodegib or a hedgehog pathway inhibitor; must stop at least 3 months prior to visit
- •Taking any topical treatment on their BCC tumors; must stop at least 1 month prior.
- •Taking Vitamin D or multivitamin supplements; must stop at least 1 month prior.
- •Currently undergoing treatment for other cancers with medical or radiation therapy.
- •Participants with a known hypersensitivity to 5-aminolevulinic acid or any component of the study material.
- •Participants with history of a photosensitivity disease, such as porphyria cutanea tarda.
- •Currently participating in another clinical trial.
研究组 & 干预措施
Group A: D3 prior to first PDT
In both groups, one PDT session is preceded by neoadjuvant PDT while the other PDT session has no pretreatment.
Group A will take dietary D3 pills prior to the first PDT treatment (day 1), and placebo pills prior to the second PDT treatment (at 2 months). Both Group A and Group B will take continuous serum D3 prior to the third PDT visit (Month 4). A final assessment of lesion clearance will be performed at 6 months
干预措施: Dietary Vitamin D3 pre-treatment (Drug)
Group A: D3 prior to first PDT
In both groups, one PDT session is preceded by neoadjuvant PDT while the other PDT session has no pretreatment.
Group A will take dietary D3 pills prior to the first PDT treatment (day 1), and placebo pills prior to the second PDT treatment (at 2 months). Both Group A and Group B will take continuous serum D3 prior to the third PDT visit (Month 4). A final assessment of lesion clearance will be performed at 6 months
干预措施: Photodynamic therapy (Radiation)
Group A: D3 prior to first PDT
In both groups, one PDT session is preceded by neoadjuvant PDT while the other PDT session has no pretreatment.
Group A will take dietary D3 pills prior to the first PDT treatment (day 1), and placebo pills prior to the second PDT treatment (at 2 months). Both Group A and Group B will take continuous serum D3 prior to the third PDT visit (Month 4). A final assessment of lesion clearance will be performed at 6 months
干预措施: Serum Maintenance Vitamin D3 (Drug)
Group B: D3 prior to second PDT visit
In both groups, one PDT session is preceded by neoadjuvant PDT while the other PDT session has no pretreatment.
Group B will receive placebo prior to their first PDT visit (day 1), and Vitamin D3 prior to their second PDT visit (at 2 months). Both Group A and Group B will take continuous D3 prior to the third PDT visit (Month 4). A final assessment of lesion clearance will be performed at 6 months
干预措施: Dietary Vitamin D3 pre-treatment (Drug)
Group B: D3 prior to second PDT visit
In both groups, one PDT session is preceded by neoadjuvant PDT while the other PDT session has no pretreatment.
Group B will receive placebo prior to their first PDT visit (day 1), and Vitamin D3 prior to their second PDT visit (at 2 months). Both Group A and Group B will take continuous D3 prior to the third PDT visit (Month 4). A final assessment of lesion clearance will be performed at 6 months
干预措施: Photodynamic therapy (Radiation)
Group B: D3 prior to second PDT visit
In both groups, one PDT session is preceded by neoadjuvant PDT while the other PDT session has no pretreatment.
Group B will receive placebo prior to their first PDT visit (day 1), and Vitamin D3 prior to their second PDT visit (at 2 months). Both Group A and Group B will take continuous D3 prior to the third PDT visit (Month 4). A final assessment of lesion clearance will be performed at 6 months
干预措施: Serum Maintenance Vitamin D3 (Drug)
结局指标
主要结局
BCC: Rate of tumor clearance
时间窗: Up to 6 months after first treatment visit
Change in tumor diameter per month. For each participant, the investigators will analyze the difference in tumor clearance between treatments, one with neoadjuvant D3+PDT, the other with PDT alone, and the other with or without D3 in order to establish a D3 replete state. The order of the first two treatments is randomized in case the assumption of a linear tumor clearance rate is incorrect The statistical significance of the difference in Delta-T after D3+PDT versus the difference in Delta-T after PDT alone will be tested using ANOVA.
次要结局
- BCC: Level of protoporphyrin IX (PpIX) accumulation in BCC lesions(Up to 6 months after first treatment visit)
- Serum 25-hydroxy-vitamin D3 (25OH-D3) levels(Up to 6 months after first treatment visit)
- Number of patients with active form of leukocyte DNA vitamin D Receptor (VDR)(Up to 6 months after first treatment visit)
- Pain scale measurement(Up to 6 months after first treatment visit)
- Erythema score(Up to 6 months after first treatment visit)
- Satisfaction with treatment outcome from the technique(Up to 6 months after first treatment visit)
- Satisfaction with cosmetic outcome from the technique(Up to 6 months after first treatment visit)