Photodynamic Therapy Using Aminolevulinic Acid in Treating Patients With Oral Leukoplakia

National Cancer Institute (NCI)

Status and phase

Terminated

Phase 1

Conditions

Oral Leukoplakia

Treatments

Other: laboratory biomarker analysis

Drug: photodynamic therapy

Drug: aminolevulinic acid hydrochloride

Study type

Interventional

Funder types

NIH

Identifiers

NCT00571558

NCI-2009-00842 (Registry Identifier)

P30CA060553 (U.S. NIH Grant/Contract)

NU-NWU05-5-01 (Other Identifier)

NWU05-5-01 (Other Identifier)

CDR0000579270

Details and patient eligibility

About

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.

Full 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.

Enrollment

15 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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