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

Primary Purpose

Basal Cell Carcinoma, Basal Cell Nevus Syndrome

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dietary Vitamin D3 pre-treatment
Photodynamic therapy
Serum Maintenance Vitamin D3
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Basal Cell Carcinoma focused on measuring Vitamin D, Photodynamic Therapy

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Medical Dermatology Specialists PhoenixRecruiting
  • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A: D3 prior to first PDT

Group B: D3 prior to second PDT visit

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

BCC: Level of protoporphyrin IX (PpIX) accumulation in BCC 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.
Serum 25-hydroxy-vitamin D3 (25OH-D3) levels
Using a 10mL blood sample, a 25OH-D3 assay will be used to determine D3 levels in the blood
Number of patients with active form of leukocyte DNA vitamin D Receptor (VDR)
Study team will collect patients' leukocyte DNA and examine the VDR gene sequences directly. Patients with the active VDR allele are postulated to have better PDT outcomes
Pain scale measurement
average pain scale measurements to assess tolerability of the technique to be taken in the week following each PDT treatment (3 total). Ranging from 0 to 10 where 0 indicates no pain and 10 indicates the worst pain possible
Erythema score
A measure of Patient Satisfaction Score. Score from photographs on a scale from 1-4 with higher scores indicating more erythema
Satisfaction with treatment outcome from the technique
A participant 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 to Extremely Dissatisfied)
Satisfaction with cosmetic outcome from the technique
A participant 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 to Extremely Dissatisfied)

Full Information

First Posted
March 12, 2018
Last Updated
October 4, 2023
Sponsor
Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03467789
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2018 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
May 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basal Cell Carcinoma, Basal Cell Nevus Syndrome
Keywords
Vitamin D, Photodynamic Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantCare ProviderInvestigator
Masking Description
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
Allocation
Randomized
Enrollment
37 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A: D3 prior to first PDT
Arm Type
Experimental
Arm Description
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
Arm Title
Group B: D3 prior to second PDT visit
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Dietary Vitamin D3 pre-treatment
Intervention 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. 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
Intervention Type
Radiation
Intervention Name(s)
Photodynamic therapy
Other Intervention Name(s)
PDT
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Serum Maintenance Vitamin D3
Intervention Description
2,000 IU/d for adults, 1,000 IU/d for children taken after third visit.
Primary Outcome Measure Information:
Title
BCC: Rate of tumor clearance
Description
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.
Time Frame
Up to 6 months after first treatment visit
Secondary Outcome Measure Information:
Title
BCC: Level of protoporphyrin IX (PpIX) accumulation in BCC lesions
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.
Time Frame
Up to 6 months after first treatment visit
Title
Serum 25-hydroxy-vitamin D3 (25OH-D3) levels
Description
Using a 10mL blood sample, a 25OH-D3 assay will be used to determine D3 levels in the blood
Time Frame
Up to 6 months after first treatment visit
Title
Number of patients with active form of leukocyte DNA vitamin D Receptor (VDR)
Description
Study team will collect patients' leukocyte DNA and examine the VDR gene sequences directly. Patients with the active VDR allele are postulated to have better PDT outcomes
Time Frame
Up to 6 months after first treatment visit
Title
Pain scale measurement
Description
average pain scale measurements to assess tolerability of the technique to be taken in the week following each PDT treatment (3 total). Ranging from 0 to 10 where 0 indicates no pain and 10 indicates the worst pain possible
Time Frame
Up to 6 months after first treatment visit
Title
Erythema score
Description
A measure of Patient Satisfaction Score. Score from photographs on a scale from 1-4 with higher scores indicating more erythema
Time Frame
Up to 6 months after first treatment visit
Title
Satisfaction with treatment outcome from the technique
Description
A participant 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 to Extremely Dissatisfied)
Time Frame
Up to 6 months after first treatment visit
Title
Satisfaction with cosmetic outcome from the technique
Description
A participant 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 to Extremely Dissatisfied)
Time Frame
Up to 6 months after first treatment visit

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Edward V. Maytin, MD, PhD
Phone
1-866-223-8100
Email
TaussigResearch@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward V. Maytin, MD, PhD
Organizational Affiliation
Cleveland Clinic, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Dermatology Specialists Phoenix
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalie Zeitouni,, M.D.C.M., FRCPC
Email
nathaliezeitouni@email.arizona.edu
Facility Name
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edward V. Maytin, MD, PhD
Phone
866-223-8100
Email
TaussigResearch@ccf.org
First Name & Middle Initial & Last Name & Degree
Edward V. Maytin, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

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

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