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Photodynamic Therapy, Gliolan, and Vitamin D3 for the Treatment of Carcinoma In-situ, High-Grade Anal Dyplasia, or Microinvasive Anal Cancer

Trial Status: Active

This phase I trial studies the side effects and best dose of the light used in photodynamic therapy and how well it works with Gliolan and vitamin D3 in the treatment of patients with carcinoma in-situ (tumors that may become cancer), high-grade anal dysplasia, or microinvasive anal cancer. Photodynamic therapy uses a drug, such as Gliolan, that becomes active when it is exposed to light. The activated drug may kill tumor cells. Vitamin D3 is a type of steroid hormone that may help enhance or restore the immune system after undergoing PDT. It is not yet known if photodynamic therapy, Gliolan, and vitamin D3 may work better in treating patients with carcinoma in-situ, high-grade anal dysplasia, or microinvasive anal cancer.

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 human immunodeficiency virus (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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • 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 > 2 x 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 fluorouracil (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

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE
Contact: Keith A. Cengel
Phone: 215-662-3932

PRIMARY OBJECTIVE:

I. To determine dose-limiting toxicities and maximum tolerated light dose in conjunction with 5-aminolevulinic acid (ALA) in photodynamic therapy and cholecalciferol (vitamin D3) supplementation for pre-malignant anal lesions.

SECONDARY OBJECTIVES:

I. To generate preliminary estimates of efficacy as measured by clearance of the dysplastic lesion(s).

II. To generate preliminary estimates of human papillomavirus (HPV) clearance rates.

III. To examine the light fluence distribution and optical properties among treated patient population.

OUTLINE: This is a dose-escalation trial of the light used in photodynamic therapy (PDT).

Patients receive cholecalciferol orally (PO) twice daily (BID) 3 days prior to through 14 weeks after PDT. Patients also receive oral aminolevulinic acid hydrochloride PO 4-6 hours prior to undergoing PDT. Patients then undergo PDT.

After completion of study treatment, patients are followed up for 30 days, then every 3 months for 24 months.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Pennsylvania / Abramson Cancer Center

Principal Investigator
Keith A. Cengel

  • Primary ID UPCC 08216
  • Secondary IDs NCI-2019-08817
  • Clinicaltrials.gov ID NCT02698293