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Trial record 3 of 8 for:    maytin

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

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ClinicalTrials.gov Identifier: NCT03467789
Recruitment Status : Recruiting
First Posted : March 16, 2018
Last Update Posted : December 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE March 12, 2018
First Posted Date  ICMJE March 16, 2018
Last Update Posted Date December 6, 2018
Actual Study Start Date  ICMJE October 1, 2018
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
Rate of tumor clearance [ Time Frame: Up to 6 months after first treatment visit ]
Change in tumor diameter per month. 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03467789 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
  • Level of protoporphyrin IX (PpIX) accumulation in BCC lesions, in the presence of neoadjuvant D3 [ Time Frame: Up to 6 months after first treatment visit ]
    Fluorescence dosimetry measurements of PpIX photo absorption with Vitamin D3
  • Level of protoporphyrin IX (PpIX) accumulation in BCC lesions, in the absence of neoadjuvant D3 [ Time Frame: Up to 6 months after first treatment visit ]
    Fluorescence dosimetry measurements of PpIX photo absorption without Vitamin D3
  • Serum 25-hydroxy-vitamin D3 (25OH-D3) levels [ Time Frame: Up to 6 months after first treatment visit ]
    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) [ Time Frame: Up to 6 months after first treatment visit ]
    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 [ Time Frame: Up to 6 months after first treatment visit ]
    average pain scale measurements to assess tolerability of the technique. Ranging from 0 to 10 where 0 indicates no pain and 10 indicates the worst pain possible
  • Number of patient symptoms [ Time Frame: Up to 6 months after first treatment visit ]
    A measure of Patient Satisfaction Score. Number of symptoms reported by patients in the week following PDT treatment
  • Erythema score [ Time Frame: Up to 6 months after first treatment visit ]
    A measure of Patient Satisfaction Score. Score from photographs on a scale from 1-4 with higher scores indicating more erythema
Original Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • Level of protoporphyrin IX (PpIX) accumulation in BCC lesions, in the presence of neoadjuvant D3 [ Time Frame: Up to 6 months after first treatment visit ]
    Fluorescence dosimetry measurements of PpIX photo absorption with Vitamin D3
  • Level of protoporphyrin IX (PpIX) accumulation in BCC lesions, in the absence of neoadjuvant D3 [ Time Frame: Up to 6 months after first treatment visit ]
    Fluorescence dosimetry measurements of PpIX photo absorption without Vitamin D3
  • Serum 25-hydroxy-vitamin D3 (25OH-D3) levels [ Time Frame: Up to 6 months after first treatment visit ]
    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) [ Time Frame: Up to 6 months after first treatment visit ]
    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 [ Time Frame: Up to 6 months after first treatment visit ]
    average pain scale measurements to assess tolerability of the technique. Ranging from 0 to 10 where 0 indicates no pain and 10 indicates the worst pain possible
  • Patient Satisfaction Score [ Time Frame: Up to 6 months after first treatment visit ]
    Score on study specific patient satisfaction scale
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma
Official Title  ICMJE Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma in Basal Cell Nevus Syndrome
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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
Primary Purpose: Treatment
Condition  ICMJE
  • Basal Cell Carcinoma
  • Basal Cell Nevus Syndrome
Intervention  ICMJE
  • Dietary Supplement: Vitamin D3 prior to first visit
    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.
  • Dietary Supplement: Vitamin D3 prior to second visit
    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.
  • Radiation: Photodynamic therapy
    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
  • Dietary Supplement: Maintenance Vitamin D3
    2,000 IU/d for adults, 1,000 IU/d for children taken after third visit.
Study Arms  ICMJE
  • Experimental: Group A: D3 prior to first PDT
    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.
    Interventions:
    • Dietary Supplement: Vitamin D3 prior to first visit
    • Radiation: Photodynamic therapy
    • Dietary Supplement: Maintenance Vitamin D3
  • Experimental: Group B: D3 prior to second PDT visit
    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.
    Interventions:
    • Dietary Supplement: Vitamin D3 prior to second visit
    • Radiation: Photodynamic therapy
    • Dietary Supplement: Maintenance Vitamin D3
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 12, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Edward V. Maytin, MD, PhD 216-445-6676 maytine@ccf.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03467789
Other Study ID Numbers  ICMJE CASE5617
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Edward V. Maytin, MD, PhD Cleveland Clinic, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP