Description:
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.
Title
- Brief Title: Vitamin D and Photodynamic Therapy for Treatment of BCC in BCNS
- Official Title: Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma in Basal Cell Nevus Syndrome
Clinical Trial IDs
- ORG STUDY ID:
18-310
- NCT ID:
NCT03483441
Conditions
- Basal Cell Nevus Syndrome
- Basal Cell Carcinoma
Interventions
| Drug | Synonyms | Arms |
|---|
| PDT | photodynamic therapy | Placebo pill prior to PDT |
Purpose
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.
Detailed 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Placebo pill prior to PDT | Placebo Comparator | BCC tumors will be treated with ALA-PDT, without any active pretreatment | |
| Vitamin D pill prior to PDT | Active Comparator | Patients will take oral Vit D supplements (10,000 IU/day) immediately prior to PDT of their BCC tumors. | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | N/A |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | BCC: Rate of Tumor Clearance |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | BCC: level of PpIX accumulation in lesions |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | ALA-PDT: Participant pain experienced from the technique |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | ALA-PDT: Participant erythema experienced from the technique |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | ALA-PDT: Satisfaction with treatment outcome from the technique |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | 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) |
| Measure: | ALA-PDT: Satisfaction with cosmetic outcome from the technique |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Vitamin D levels |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | Vitamin D level (25-hydroxy-cholecalciferol) measured in serum |
| Measure: | Allele polymorphisms in the gene of the Vitamin D receptor (VDR) |
| Time Frame: | Selected Visits (6 months total) |
| Safety Issue: | |
| Description: | Identify the allele combination present at VDR locus |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | The Cleveland Clinic |
Last Updated
November 20, 2020
