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

NCT03467789 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE5617
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

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).

Conditions

Basal Cell Carcinoma; Basal Cell Nevus Syndrome

Keywords

Vitamin D; Photodynamic Therapy

Outcome Measures

Primary Outcomes (1)

• BCC: Rate of tumor clearance

  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.

  Up to 6 months after first treatment visit

Secondary Outcomes (7)

• 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

Study Arms (2)

Group A: D3 prior to first PDT

EXPERIMENTAL

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

Drug: Dietary Vitamin D3 pre-treatment; Radiation: Photodynamic therapy; Drug: Serum Maintenance Vitamin D3

Group B: D3 prior to second PDT visit

EXPERIMENTAL

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

Drug: Dietary Vitamin D3 pre-treatment; Radiation: Photodynamic therapy; Drug: Serum Maintenance Vitamin D3

Interventions

Dietary Vitamin D3 pre-treatment DRUG

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. Duration of pretreatment will be 14 days if the D3 level is \< 31 ng/mL, and 5 days if the D3 level is \> 31 ng/mL

Group A: D3 prior to first PDT; Group B: D3 prior to second PDT visit

Photodynamic therapy RADIATION

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

Also known as: PDT

Group A: D3 prior to first PDT; Group B: D3 prior to second PDT visit

Serum Maintenance Vitamin D3 DRUG

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

Group A: D3 prior to first PDT; Group B: D3 prior to second PDT visit

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

Medical Dermatology Specialists Phoenix

Phoenix, Arizona, 85006, United States

Location

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Carcinoma, Basal Cell; Basal Cell Nevus Syndrome

Interventions

Photochemotherapy; 1-phenyl-3,3-dimethyltriazene

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Study Officials

• Edward V. Maytin, MD, PhD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 16, 2018
• Study Start: October 1, 2018
• Primary Completion: January 6, 2023
• Study Completion: January 6, 2023
• Last Updated: October 17, 2024

Record last verified: 2024-10

Locations

US (2)