Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma in Basal Cell Nevus Syndrome

Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma

Sponsors

Lead sponsor: Case Comprehensive Cancer Center

Collaborator: National Cancer Institute (NCI)

Source Case Comprehensive Cancer Center
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.

Overall Status Recruiting
Start Date October 1, 2018
Completion Date November 2021
Primary Completion Date November 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Rate of tumor clearance Up to 6 months after first treatment visit
Secondary Outcome
Measure Time Frame
Level of protoporphyrin IX (PpIX) accumulation in BCC lesions, in the presence of neoadjuvant D3 Up to 6 months after first treatment visit
Level of protoporphyrin IX (PpIX) accumulation in BCC lesions, in the absence of neoadjuvant D3 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
Number of patient symptoms Up to 6 months after first treatment visit
Erythema score Up to 6 months after first treatment visit
Enrollment 50
Condition
Intervention

Intervention type: Dietary Supplement

Intervention name: Vitamin D3 prior to first visit

Description: The daily dose of D3 will always be 10,000 IU/day. 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.

Arm group label: Group A: D3 prior to first PDT

Intervention type: Dietary Supplement

Intervention name: Vitamin D3 prior to second visit

Description: The daily dose of D3 will always be 10,000 IU/day. 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.

Arm group label: Group B: D3 prior to second PDT visit

Intervention type: Radiation

Intervention name: Photodynamic therapy

Description: Photodynamic Therapy (PDT) is an experimental technique that works by combining a photosensitizing topical agent and an intense light source to kill tumor cells.

Other name: PDT

Intervention type: Dietary Supplement

Intervention name: Maintenance Vitamin D3

Description: 2,000 IU/d for adults, 1,000 IU/d for children taken after third visit.

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 patient 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 1 month prior.

- Taking any topical treatment on their BCC tumors; must stop at least one month prior.

- Taking Vitamin D or multivitamin supplements; must stop at least one month prior.

- Currently undergoing treatment for other cancers with medical or radiation therapy.

- Patients with a known hypersensitivity to 5-aminolevulinic acid or any component of the study material.

- Patients with history of a photosensitivity disease, such as porphyria cutanea tarda.

- Currently participating in another clinical trial.

Gender: All

Minimum age: N/A

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Edward V. Maytin, MD, PhD Principal Investigator Cleveland Clinic, Case Comprehensive Cancer Center
Overall Contact

Last name: Edward V. Maytin, MD, PhD

Phone: 216-445-6676

Email: [email protected]

Location
facility status contact investigator Cleveland Clinic, Case Comprehensive Cancer Center Edward Maytin, MD, PhD 216-445-6676 [email protected] Edward Maytin, MD, PhD Principal Investigator
Location Countries

United States

Verification Date

December 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Group A: D3 prior to first PDT

Arm group type: Experimental

Description: Group A will take D3 pills prior to the first PDT treatment, and placebo pills prior to the second PDT treatment. Both Group A and Group B will take no study drug prior to their third PDT visit.

Arm group label: Group B: D3 prior to second PDT visit

Arm group type: Experimental

Description: GROUP B will receive placebo prior to their first PDT visit, and Vitamin D3 prior to their second PDT visit. Both Group A and Group B will take no study drug prior to their third PDT visit.

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Double (Participant, Care Provider)

Masking description: The study will be double-blinded. Neither the patient 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

Source: ClinicalTrials.gov