Photodynamic Therapy Using Aminolevulinic Acid in Treating Patients With Oral Leukoplakia

Oral Leukoplakia Clinical Trial

Official title:

Phase I Study of Photodynamic Therapy Using Pulsed Dye Laser and Oral Aminolevulinic Acid in Patients With Oral Leukoplakia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00571558
• Other study ID #: NCI-2009-00842
• Secondary ID: NCI-2009-00842CD
• Status: Terminated
• Phase: Phase 1
• First received: December 11, 2007
• Last updated: October 8, 2014
• Start date: March 2008
• Est. completion date: November 2010

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase I trial studies the side effects and best dose of photodynamic therapy using aminolevulinic acid in treating patients with oral leukoplakia. Photodynamic therapy uses a drug, such as aminolevulinic acid, that becomes active when it is exposed to a certain kind of light. When the drug is active, abnormal cells are killed. Photodynamic therapy using aminolevulinic acid may be effective against oral leukoplakia.

Description:

PRIMARY OBJECTIVES:

I. To determine the toxicity and feasibility of photodynamic therapy using pulsed laser therapy and oral aminolevulinic acid in treating patients with oral leukoplakia.

II. To define the dose-limiting toxicity and maximum tolerated dose of photodynamic therapy using pulsed laser therapy and oral aminolevulinic acid in these patients.

SECONDARY OBJECTIVES:

I. To assess the efficacy of photodynamic therapy using pulsed dye laser and oral aminolevulinic acid by examining clinical response at 1 and 3 months.

II. To determine quantitative histologic response at 3 months. III. To explore the association of response with specific molecular and biologic markers (i.e., DNA ploidy, proliferation using Ki-67, apoptosis using TUNEL, cyclin D1, and p53).

OUTLINE: This is a dose-escalation study of long pulsed dye laser light.

Patients receive aminolevulinic acid* orally (PO) 3-4 hours before undergoing photodynamic therapy using pulsed dye laser on day 1.

(Note: *Patients in cohort 1 and a latter cohort [to be determined during the course of the study] do not receive aminolevulinic acid before photodynamic therapy.)

Patients undergo biopsies of target lesions and clinically uninvolved mucosa 4-8 weeks before beginning therapy and then at 3 months for biomarker studies (DNA ploidy, p53, Ki-67, cyclin D1, and TUNEL assay). Blood is collected on days 1, 2, 14, 28, and 84 for toxicity assessment.

After completion of study treatment, patients are followed for up to 84 days.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: November 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Criteria:

• Histologically confirmed oral leukoplakia with dysplasia OR oral leukoplakia with hyperplasia in a high-risk area (e.g., floor of mouth, tongue, or oropharynx)

• Multiple oral leukoplakia lesions are allowed however no more than 5 distinct lesions are biopsied and treated

• All lesions to be treated must be technically accessible by laser

• Patients with oral leukoplakia with hyperplasia in a non-high-risk location (e.g., buccal mucosa from ill-fitting dentures) are not allowed

• Must be willing to undergo baseline biopsies of leukoplakia lesion(s) and surrounding normal tissue 4-8 weeks before therapy and repeat biopsies at 3 months

• No evidence of ongoing radiation damage to the target site

• Karnofsky performance status (PS) 70-100% or Zubrod PS 0-1

• Life expectancy > 2 years

• Hemoglobin > 12 g/dL

• Platelet count > 100,000/mm^3

• ANC > 1,500/mm^3

• Creatinine =< 1.5 mg/dL

• SGPT and SGOT =< 1.5 x upper limit of normal (ULN)

• Total bilirubin =< 1.5 x ULN (a higher level of bilirubin due to a familial metabolism will be considered on an individual basis)

• Willing to adhere to avoidance of sunlight and indoor light exposure for 24 hours after treatment

• Not pregnant or nursing

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to aminolevulinic acid

• No porphyria

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situation that, in the opinion of the investigators, would limit compliance or jeopardize the patient or integrity of the data

• Prior treatment for leukoplakia allowed

• No prior photodynamic therapy

• More than 3 months since prior participation in a clinical trial for leukoplakia

• More than 4 weeks since prior ablative therapy to the target lesion

• More than 4 weeks since prior and no concurrent psoralen or PUVA therapy

• No concurrent oral retinoids (e.g., isotretinoin)

• No concurrent use of tanning beds

• No other concurrent investigational agents

• Fertile patients must use effective contraception

• Patients with a previous diagnosis of stage I or II head and neck cancer are eligible provided definitive therapy, including radiation therapy, is completed and the patient has been rendered disease free for >= 2 years

• No chronic liver disease including those with normal liver function tests

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukoplakia
• Leukoplakia, Oral
• Oral Leukoplakia

Intervention

Drug:
• aminolevulinic acid hydrochloride
Given PO
• photodynamic therapy
Undergo photodynamic therapy

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability with determination of optimal light dosing regimen, determination of dose limiting-toxicities, and maximum tolerated dose of photodynamic therapy using pulsed laser therapy and oral aminolevulinic acid		Up to 84 days	Yes
Secondary	Clinical response		1 month	No
Secondary	Clinical response		3 months	No
Secondary	Histologic response		3 months	No
Secondary	Mucosal risk marker modulation as measured by proliferation using Ki-67, apoptosis using TUNEL, cyclin D1, p53 expression, and DNA ploidy		Up to 84 days	No