Photodynamic Therapy Using Aminolevulinic Acid in Treating Patients With Oral Leukoplakia

This study has been terminated.
(NCI decision not to continue equipment lease.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00571558
First received: December 11, 2007
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Oral Leukoplakia
Drug: aminolevulinic acid hydrochloride
Drug: photodynamic therapy
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Photodynamic Therapy Using Pulsed Dye Laser and Oral Aminolevulinic Acid in Patients With Oral Leukoplakia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 84 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical response [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Clinical response [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Histologic response [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Mucosal risk marker modulation as measured by proliferation using Ki-67, apoptosis using TUNEL, cyclin D1, p53 expression, and DNA ploidy [ Time Frame: Up to 84 days ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: March 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (aminolevulinin acid and photodynamic therapy)
Patients receive aminolevulinic acid PO 3-4 hours before undergoing photodynamic therapy using pulsed dye laser on day 1.
Drug: aminolevulinic acid hydrochloride
Given PO
Other Names:
  • 5-ALA HCl
  • ALA HCl
  • aminolevulinic acid HCl
Drug: photodynamic therapy
Undergo photodynamic therapy
Other Names:
  • Light Infusion Therapy™
  • PDT
  • therapy, photodynamic
Other: laboratory biomarker analysis
Correlative studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571558

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Investigators
Principal Investigator: Wong Stuart Robert H. Lurie Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00571558     History of Changes
Other Study ID Numbers: NCI-2009-00842, NU-NWU05-5-01, CDR0000579270, P30CA06055
Study First Received: December 11, 2007
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukoplakia
Leukoplakia, Oral
Precancerous Conditions
Neoplasms
Pathological Conditions, Anatomical
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Aminolevulinic Acid
Photosensitizing Agents
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 18, 2014