Clinical trial NCT03467789: Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma
Official title: Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma in Basal Cell Nevus Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Basal Cell Carcinoma
Basal Cell Nevus Syndrome
Keywords: Vitamin D
Photodynamic Therapy
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2018-03-16
Enrollment: 37
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each patient serves as his/her own control. Two PDT sessions are given, constituting Arm 1 and Arm 2. Arm 1 is placebo pill, then PDT. Arm 2 is Vit D pill, then PDT. In any given patient, the order of Arm 1 vs. Arm 2 will be randomized.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Study Design:

In this clinical study, each patient will serve as his or her own control with respect to BCC tumor responsiveness to neoadjuvant D3 supplementation. The first two PDT treatments will be randomized. Thus, patients in Group A will take D3 pills prior to the first PDT treatment, and placebo pills prior to the second PDT treatment. For patients in Group B, the order is reversed. Total amounts of D3 supplementation given will be adjusted, based upon serum 25-hydroxy-D3 levels found at baseline. Patients with VD deficiency will take 14 days of neoadjuvant D3, vs. only 5 days if the initial VD level is normal.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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 1.
* 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.

Primary outcomes:
measure: BCC: Rate of tumor clearance
timeFrame: Up to 6 months after first treatment visit
Secondary outcomes:
measure: BCC: Level of protoporphyrin IX (PpIX) accumulation in BCC lesions
timeFrame: Up to 6 months after first treatment visit
measure: Serum 25-hydroxy-vitamin D3 (25OH-D3) levels
timeFrame: Up to 6 months after first treatment visit
measure: Number of patients with active form of leukocyte DNA vitamin D Receptor (VDR)
timeFrame: Up to 6 months after first treatment visit
measure: Pain scale measurement
timeFrame: Up to 6 months after first treatment visit
measure: Erythema score
timeFrame: Up to 6 months after first treatment visit
measure: Satisfaction with treatment outcome from the technique
timeFrame: Up to 6 months after first treatment visit
measure: Satisfaction with cosmetic outcome from the technique
timeFrame: Up to 6 months after first treatment visit
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Medical Dermatology Specialists Phoenix
state: Arizona
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic, Case Comprehensive Cancer Center
name: Edward V. Maytin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: