Vitamin D and Photodynamic Therapy for Treatment of BCC in BCNS

Basal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03483441
• Other study ID #: 18-310
• Status: Recruiting
• Phase: Phase 1
• Start date: October 1, 2018
• Est. completion date: May 1, 2023

Study information

• Verified date: November 2020
• Source: The Cleveland Clinic
• Contact: Jeff Negrey, MA
• Phone: 216-636-5504
• Email: negreyj2[@]ccf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research is to evaluate the use of Photodynamic Therapy (PDT) to treat the multiple basal cell carcinoma (BCC) skin cancers in children and adults with Basal Cell Nevus Syndrome (or who have at least 3 BCC tumors present). In addition, the investigators will test a hypothesis (based upon our extensive preclinical studies in mice) that induction of a transient spike in serum Vitamin D levels through administration of dietary Vitamin D (cholecalciferol; D3) can significantly increase PDT efficacy and improve the clearance of cutaneous BCC tumors.

Description:

Patients with a rare genetic syndrome, called Basal Cell Nevus Syndrome or Gorlin-Goltz Syndrome (caused by a mutation in the PTCH1 gene) will be recruited to participate in this study. Potential patients will be referred by their local physicians or by the BCCNS Life Support Network to contact a study coordinator about enrollment.

The study will examine a combination regimen of Vitamin D3/PDT and compare its efficacy in treating BCC tumors to PDT alone. The hypothesis is that oral D3 supplements, administered over a relatively short time, can boost the effectiveness of PDT for cutaneous (BCC) in this patient population. Participants will receive three PDT treatments, at two-month intervals, over a 6 month period.

Tumor clinical clearance rates after neoadjuvant Vitamin D3/PDT, versus PDT alone, will be compared within the same patient. Measurement endpoints will include tumor dimensions by clinical examination, tumor measurements in photographs, PpIX fluorescence, serum 25OH-D3 levels, and characterization of VDR gene alleles. In addition, assessments of the tolerability (pain scale measurements) and patient satisfaction with the technique will be measured.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• A diagnosis of Basal Cell Nevus Syndrome (BCNS)

• 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

Related Conditions & MeSH terms

• Basal Cell Carcinoma
• Basal Cell Nevus Syndrome
• Carcinoma
• Carcinoma, Basal Cell
• Syndrome

Intervention

Other:
• Placebo pill
An inert placebo pill will be taken for several days prior to PDT

Dietary Supplement:
• Vitamin D
10,000 units of cholecalciferol will be taken for several days prior to PDT

Drug:
• PDT
Levulan (5-aminolevulinic acid) is applied to tumors for 4 hr, then illuminated with blue light

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	Medical Dermatology Specilists	Phoenix	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
The Cleveland Clinic	Harvard Medical School, University of Arizona

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BCC: Rate of Tumor Clearance	For each patient, 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 tumor clearance after D3+PDT versus the difference in tumor clearance after PDT alone will be tested using ANOVA.	Selected Visits (6 months total)
Secondary	BCC: level of PpIX accumulation in lesions	For each patient, whether in the absence or presence of neoadjuvant Vitamin D3, assessments of PpIX accumulation in BCC lesions using fluorescence dosimetry measurements will be made at selected treatment visits.	Selected Visits (6 months total)
Secondary	ALA-PDT: Participant pain experienced from the technique	For each patient, pain scale measurements will be taken in the week following each PDT treatment. The absence/presence of pain will be recorded on a 0-to-10 visual/analog scale.	Selected Visits (6 months total)
Secondary	ALA-PDT: Participant erythema experienced from the technique	The investigators will record erythema (on a scale of 1 to 4+), from clinical exam and from the photographs, in the treated areas just prior to the second treatment in each PDT cycle.	Selected Visits (6 months total)
Secondary	ALA-PDT: Satisfaction with treatment outcome from the technique	A patient satisfaction questionnaire will be administered at the final study visit measuring the participant's satisfaction with the treatment outcome on a 5 point scale (Extremely Satisfied -> Extremely Dissatisfied)	Selected Visits (6 months total)
Secondary	ALA-PDT: Satisfaction with cosmetic outcome from the technique	A patient satisfaction questionnaire will be administered at the final study visit measuring the participant's satisfaction with the cosmetic outcome on a 5 point scale (Extremely Satisfied -> Extremely Dissatisfied)	Selected Visits (6 months total)
Secondary	Vitamin D levels	Vitamin D level (25-hydroxy-cholecalciferol) measured in serum	Selected Visits (6 months total)
Secondary	Allele polymorphisms in the gene of the Vitamin D receptor (VDR)	Identify the allele combination present at VDR locus	Selected Visits (6 months total)