Clinical Trials /

PDT Plus Vitamin D3 for Anal Dysplasia

NCT02698293

Description:

This is a phase I dose escalation study of photodynamic therapy (PDT) for the treatment of patients with pre-malignant tumors and superficial microinvasive disease of the anal canal and/or perianal skin. All subjects (a maximum of 12) will be given the photosensitizer ALA orally followed by the administration of red light (629-635 nm) to the tumor from a laser. The dose of ALA will be 40 mg/kg administered approximately 4-6 hours before light administration. There will be two levels of light dose: 50 and 100 J/cm2, 3-6 patients in each. Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT. Patients will be observed for 30 days for the development of DLT. Patients will be followed up for 24 months for additional toxicity and efficacy data collection.

Related Conditions:
  • Anal Intraepithelial Neoplasia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PDT Plus Vitamin D3 for Anal Dysplasia
  • Official Title: A Phase I Study of Photodynamic Therapy (PDT) Plus Vitamin D3 for High-grade Anal Dysplasia and Microinvasive Anal Cancer

Clinical Trial IDs

  • ORG STUDY ID: UPCC 08216
  • NCT ID: NCT02698293

Conditions

  • Anal Dysplasia
  • Carcinoma in Situ

Interventions

DrugSynonymsArms
GliolanALACohort 1
Vitamin D3 cholecalciferol)Natures Made Vitamin D3Cohort 1

Purpose

This is a phase I dose escalation study of photodynamic therapy (PDT) for the treatment of patients with pre-malignant tumors and superficial microinvasive disease of the anal canal and/or perianal skin. All subjects (a maximum of 12) will be given the photosensitizer ALA orally followed by the administration of red light (629-635 nm) to the tumor from a laser. The dose of ALA will be 40 mg/kg administered approximately 4-6 hours before light administration. There will be two levels of light dose: 50 and 100 J/cm2, 3-6 patients in each. Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT. Patients will be observed for 30 days for the development of DLT. Patients will be followed up for 24 months for additional toxicity and efficacy data collection.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1Experimental5-aminolevulinic acid hydrochloride (Gliolan), orally, 40 mg/kg administered approximately 4-6 hours before light administration. There will be two levels of light dose: 50 and 100 J/cm2. Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT. Total duration of drug product administration (including any open-label lead-in, if applicable). Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT. None This is a phase I dose escalation study, with two levels of light dose. The design is cohorts of 3s. Light at 50 Joules and Light at 100 joules There are pre-defined DLTs.
  • Gliolan
  • Vitamin D3 cholecalciferol)
Cohort 2Experimental5-aminolevulinic acid hydrochloride (Gliolan), orally, 40 mg/kg administered approximately 4-6 hours before light administration. There will be two levels of light dose: 50 and 100 J/cm2. Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT Total duration of drug product administration (including any open-label lead-in, if applicable). Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT. None This is a phase I dose escalation study, with two levels of light dose. The design is cohorts of 3s. Light at 50 Joules and Light at 100 joules There are pre-defined DLTs.
  • Gliolan
  • Vitamin D3 cholecalciferol)
Cohort 3Experimental5-aminolevulinic acid hydrochloride (Gliolan), orally, 40 mg/kg administered approximately 4-6 hours before light administration. There will be two levels of light dose: 50 and 100 J/cm2. Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT Total duration of drug product administration (including any open-label lead-in, if applicable). Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT. None This is a phase I dose escalation study, with two levels of light dose. The design is cohorts of 3s. Light at 50 Joules and Light at 100 joules There are pre-defined DLTs.
  • Gliolan
  • Vitamin D3 cholecalciferol)

Eligibility Criteria

        Inclusion Criteria

          -  A histological or cytological diagnosis of high-grade dysplasia or carcinoma in-situ,
             within past 4 months.

          -  Premalignant lesions containing focal microinvasion are eligible when:

               -  Surgery is not clinically mandated.

               -  Subjects with medical conditions precluding surgery.

               -  Subjects whose lesions cannot be completely resected based on size or location,
                  or where significant functional morbidity would be anticipated with further
                  surgery.

               -  Patients refuse surgery.

          -  The justification for inclusion of patients with microinvasive disease is based
             reports demonstrating the ability of photodynamic therapy to successfully treat both
             dysplasia and T1 squamous cell carcinoma of the anal canal

          -  HPV positive by Cobas or other cytological assays within past 4 months

          -  Documented HIV positivity

          -  Patients must be on highly active anti-retroviral therapy with a CD4 count >200 for
             the past 12 months

          -  Viral load <200 for 12 months for the past 12 months

          -  ECOG performance status of 0-1.

          -  18 years of age or older.

          -  Study subjects capable of providing informed consent.

          -  Women of childbearing potential and men must agree to use a medically accepted method
             of birth control from the time they sign consent and until one month after receiving
             ALA

        Exclusion Criteria:

          -  Study subjects in whom the lesion has invasive squamous cell carcinoma of the anal
             cavity which is clinically appreciable.

          -  Clinically occult microinvasive squamous cell carcinoma of the anal cavity which is
             not focal.

          -  Study subjects who are pregnant or lactating .

          -  Study subjects who have a platelet count of less than 100,000/cubic mm.

          -  Study subjects with elevated aspartate aminotransferase (AST), alanine
             aminotransferase (ALT), alkaline phosphatase, or total bilirubin levels >2X normal or
             a history of chronic liver disease or cirrhosis of the liver.

          -  Significant cardiovascular history that would put the study subject at risk from
             hypotension that may occur with ALA

          -  Study subjects with porphyria or hypersensitivity to porphyrins.

          -  Administration of the following compounds: tetracyclines, sulfonamides,
             fluoroquinolones within 48 hours, or hypericin extracts within a week prior to light
             administration.

          -  Study subjects with abnormal baseline creatinine level or diagnosed kidney disease.

          -  Treatment with 5-FU, Imiquimod, trichloroacetic acid or ablative therapy within the
             previous month.

          -  Study subjects who have a medical history of immune suppression. This will include
             patients with a past transplantation requiring ongoing immunosuppressive medications.

          -  A history of sarcoidosis, hyperphosphatemia, or known kidney stones
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of adverse events
Time Frame:18 months
Safety Issue:
Description:DLTs have been defined

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

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