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PDT Plus Vitamin D3 for Anal Dysplasia

Primary Purpose

Anal Dysplasia, Carcinoma in Situ

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Gliolan

Vitamin D3 cholecalciferol)

Photodynamic Therpay

About this trial

This is an interventional treatment trial for Anal Dysplasia

Eligibility Criteria

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

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

Sites / Locations

Abramson Cancer Center of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

5-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.

5-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.

Outcomes

Primary Outcome Measures

Number of adverse events

DLTs have been defined

Secondary Outcome Measures

Full Information

NCT ID

NCT02698293

First Posted

March 1, 2016

Last Updated

November 21, 2022

Sponsor

Abramson Cancer Center at Penn Medicine

1. Study Identification

Unique Protocol Identification Number

NCT02698293

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Covid-19

Study Start Date

December 1, 2019 (Actual)

Primary Completion Date

January 1, 2023 (Anticipated)

Study Completion Date

January 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Abramson Cancer Center at Penn Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anal Dysplasia, Carcinoma in Situ

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

5-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.

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

5-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.

Intervention Type

Drug

Intervention Name(s)

Gliolan

Other Intervention Name(s)

ALA

Intervention Description

orally, 40 mg/kg 4-6 hours prior to light application

Intervention Type

Drug

Intervention Name(s)

Vitamin D3 cholecalciferol)

Other Intervention Name(s)

Natures Made Vitamin D3

Intervention Description

Vitamin D3 (cholecalciferol) supplementation (10,000 IU daily) will be provided from 3 days prior through 14 weeks after light delivery for PDT.

Intervention Type

Other

Intervention Name(s)

Photodynamic Therpay

Other Intervention Name(s)

PDT

Intervention Description

Approximately 4-6 hours after photosensitizer administration, activating light will be applied. The target mucosal lesion will be identified based on the initial clinical evaluation. Treatment light will be generated using a Modulight ML7710-630-6K diode laser, This laser produces up to 6W total power, with a peak wavelength of 630nm and 90% of laser power within 630-633 nm. The light fluence (doses) will be 50 and 100 Joules per square centimeter.

Primary Outcome Measure Information:

Title

Number of adverse events

Description

DLTs have been defined

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Keith Cengel, MD, PhD

Organizational Affiliation

Abramson Cancer Center at Penn Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Abramson Cancer Center of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

PDT Plus Vitamin D3 for Anal Dysplasia

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