LeukoplakiaPhase 1/2NCT00571974
Treatment of Oral Premalignant Lesions With 5-ALA PDT
A Phase 1/2 study testing PDL-585, ScleroPLUS laser, 5-Aminolevulinic Acid (Levulan KerastickTM) and Fluorescence Diagnosis Imaging in people with Leukoplakia and Erythroplakia, run by University of Arkansas at 1 site in United States.
Trial summary
Oral leukoplakia within the mouth is a visible white patch which can develop into cancer if not treated. There is no good treatment for these lesions, apart from surgery which is associated with significant side effects and physical deformation of the treated area. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Leukoplakia, Erythroplakia
- What is being tested?
- PDL-585, ScleroPLUS laser, 5-Aminolevulinic Acid (Levulan KerastickTM) and Fluorescence Diagnosis Imaging
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Jan 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least one grossly visible premalignant lesion (i.e. leukoplakia or erythroplakia) in the oral cavity or oropharynx, with a confirmed diagnosis of leukoplakia with or without dysplasia,measuring ≥ 10 mm in diameter.
- Informed of alternative treatment methods including watchful waiting, laser ablation, or surgical resection.
- Eligible for long-term follow-up for at least one year and be able to tolerate biopsies.
- Subject has signed an informed consent.
- Subject is between the ages of 18 - 80 years of age.
- Male or Female
- Zubrod performance status of 0 or 1 at screening. See Appendix A
Who cannot join
- Known sensitivity to porphyrins or photoactive medications - See Appendix B
- Invasive carcinoma of the lesion as demonstrated by biopsy.
- Subjects with inherited or acquired blood clotting defects
- Women who are breast feeding, have a positive (+) urine pregnancy test, or refuse to use 2 effective means of contraception during drug exposure and up to 48 hours after.
- Subjects with porphyria
- Life expectancy less than 12 months
- Inability or unwillingness of subject to give written informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
About this study
Official title: A Combined Phase I/II Single Site Study to Determine the Safety and Efficacy of Photodynamic Therapy (PDT) Utilizing 5-aminolevulinic Acid (5-ALA) and PDT in the Treatment of Premalignant Oral and/or Oropharynx Lesions.
Oral leukoplakia within the mouth is a visible white patch which can develop into cancer if not treated. There is no good treatment for these lesions, apart from surgery which is associated with significant side effects and physical deformation of the treated area.
The investigators hypothesized that photodynamic therapy can be used safely and effectively to induce significant regression of oral leukoplakia.
Read the detailed description
This is a combined Phase I/II non-randomized prospective study designed to determine the safety and assess the clinical efficacy of PDT in the treatment of oral leukeplekia with 5-ALA and 585-nm PDL with 1.5 ms pulse time. In the first part of the study we determined the maximum tolerated dose (MTD) of the PDL radiant exposure in combination with 5-ALA. In the second phase of the study, this dose is used to treat subjects at the MTD in order to determine the efficacy of the treatment by documenting the regression of the treated lesions.
- Conditions
- Leukoplakia, Erythroplakia
- Being tested
- PDL-585, ScleroPLUS laser, 5-Aminolevulinic Acid (Levulan KerastickTM), Fluorescence Diagnosis Imaging
- Medical subject headings
- Leukoplakia, Erythroplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDL-585, ScleroPLUS laserDevice
PDT Treatment; emits light with 585 nm wavelength in pulses of 1.5 milliseconds in sections of 5 mm diameter to target the lesion and surrounding tissue
5-Aminolevulinic Acid (Levulan KerastickTM)Drug
Also called 5-ALA
Topically administered; incubation time 60-180 minutes; single dose (345 mg of active 5-ALA in 1.5 ml solution); soaked onto white gauze and applied to lesion, covered with sterile Xeroform gauze
Fluorescence Diagnosis ImagingProcedure or surgery
FD Image taken prior to PDL-585 usage
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 light dose escalation | Experimental | During Phase I, to determine the maximum tolerated energy density of the Pulse Dye Laser operated at 585 nm with a pulse time of 1.5 ms (PDL-585), when used in combination with 5-aminolevulinic acid (5-ALA) applied topically to the premalignant lesion.
The maximum tolerated energy density will be called the Maximum Tolerated Dose (MTD). Procedure: Fluorescence Diagnosis Imaging Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 6, 7 and 8 J/cm2. Receives: Device: PDL-585, ScleroPLUS laser; Drug: 5-Aminolevulinic Acid (Levulan KerastickTM); Procedure: Fluorescence Diagnosis Imaging |
| Phase 2 - Treatment efficacy of PDT | Experimental | Procedure: Fluorescence Diagnosis Imaging
Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 8 J/cm2. Receives: Device: PDL-585, ScleroPLUS laser; Drug: 5-Aminolevulinic Acid (Levulan KerastickTM); Procedure: Fluorescence Diagnosis Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
The traditional 3+3 dose escalation design was employed. Three cohorts were enrolled at 3 subjects per cohort, and treated with escalating radiant exposures of 6, 7, or 8 J/cm2. In each cohort, the number of dose-limiting toxicities (DLTs) were observed. Dose escalation rules were the same as those provided by Storer 1989.
Measured: Day 2
The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR).
The response rate was quantified by examination by an experienced head and neck surgeon and classified as follows: significant response (SR) was one where the lesion had greater than 75% resolution, partial response (PR) was one in which the lesion was reduced in size by at least 25%, and no response (NR) was one where the lesion was reduced by less than 25% in size.
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2007 (estimated)
- Study startJan 2007
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukoplakiaStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gal Shafirstein, PhD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00571974
- Sponsor's protocol ID
- 51439
- Status last verified
- Mar 2015
- First submitted
- 5 Dec 2007
- Last updated
- 24 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Shafirstein G, Friedman A, Siegel E, Moreno M, Baumler W, Fan CY, Morehead K, Vural E, Stack BC Jr, Suen JY. Using 5-aminolevulinic acid and pulsed dye laser for photodynamic treatment of oral leukoplakia. Arch Otolaryngol Head Neck Surg. 2011 Nov;137(11):1117-23. doi: 10.1001/archoto.2011.178.
PubMed 22106236
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Combined Phase I/II Single Site Study to Determine the Safety and Efficacy of Photodynamic Therapy (PDT) Utilizing 5-aminolevulinic Acid (5-ALA) and PDT in the Treatment of Premalignant Oral and/or Oropharynx Lesions.
- ClinicalTrials.gov ID
- NCT00571974
- Acronym / sponsor ID
- 51439
- Conditions
- Leukoplakia, Erythroplakia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 12 Dec 2007 (estimated)
- Results
- Posted 13 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Oral leukoplakia within the mouth is a visible white patch which can develop into cancer if not treated. There is no good treatment for these lesions, apart from surgery which is associated with significant side effects and physical deformation of the treated area.
The investigators hypothesized that photodynamic therapy can be used safely and effectively to induce significant regression of oral leukoplakia.
Detailed description
This is a combined Phase I/II non-randomized prospective study designed to determine the safety and assess the clinical efficacy of PDT in the treatment of oral leukeplekia with 5-ALA and 585-nm PDL with 1.5 ms pulse time. In the first part of the study we determined the maximum tolerated dose (MTD) of the PDL radiant exposure in combination with 5-ALA. In the second phase of the study, this dose is used to treat subjects at the MTD in order to determine the efficacy of the treatment by documenting the regression of the treated lesions.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 light dose escalation | Experimental | Device: PDL-585, ScleroPLUS laser, Drug: 5-Aminolevulinic Acid (Levulan KerastickTM), Procedure: Fluorescence Diagnosis ImagingDuring Phase I, to determine the maximum tolerated energy density of the Pulse Dye Laser operated at 585 nm with a pulse time of 1.5 ms (PDL-585), when used in combination with 5-aminolevulinic acid (5-ALA) applied topically to the premalignant lesion. The maximum tolerated energy density will be called the Maximum Tolerated Dose (MTD). Procedure: Fluorescence Diagnosis Imaging Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 6, 7 and 8 J/cm2. |
| Phase 2 - Treatment efficacy of PDT | Experimental | Device: PDL-585, ScleroPLUS laser, Drug: 5-Aminolevulinic Acid (Levulan KerastickTM), Procedure: Fluorescence Diagnosis ImagingProcedure: Fluorescence Diagnosis Imaging Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 8 J/cm2. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- At least one grossly visible premalignant lesion (i.e. leukoplakia or erythroplakia) in the oral cavity or oropharynx, with a confirmed diagnosis of leukoplakia with or without dysplasia,measuring ≥ 10 mm in diameter.
- Informed of alternative treatment methods including watchful waiting, laser ablation, or surgical resection.
- Eligible for long-term follow-up for at least one year and be able to tolerate biopsies.
- Subject has signed an informed consent.
- Subject is between the ages of 18 - 80 years of age.
Key exclusion criteria (7 listed)
- Known sensitivity to porphyrins or photoactive medications - See Appendix B
- Invasive carcinoma of the lesion as demonstrated by biopsy.
- Subjects with inherited or acquired blood clotting defects
- Women who are breast feeding, have a positive (+) urine pregnancy test, or refuse to use 2 effective means of contraception during drug exposure and up to 48 hours after.
- Subjects with porphyria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PDL-585, ScleroPLUS laserPDT Treatment; emits light with 585 nm wavelength in pulses of 1.5 milliseconds in sections of 5 mm diameter to target the lesion and surrounding tissue | Device | Phase 1 light dose escalation, Phase 2 - Treatment efficacy of PDT |
| 5-Aminolevulinic Acid (Levulan KerastickTM)Also: 5-ALATopically administered; incubation time 60-180 minutes; single dose (345 mg of active 5-ALA in 1.5 ml solution); soaked onto white gauze and applied to lesion, covered with sterile Xeroform gauze | Drug | Phase 1 light dose escalation, Phase 2 - Treatment efficacy of PDT |
| Fluorescence Diagnosis ImagingFD Image taken prior to PDL-585 usage | Procedure or surgery | Phase 1 light dose escalation, Phase 2 - Treatment efficacy of PDT |
Primary outcome
Maximum Tolerated Dose
Time frame: Day 2
The traditional 3+3 dose escalation design was employed. Three cohorts were enrolled at 3 subjects per cohort, and treated with escalating radiant exposures of 6, 7, or 8 J/cm2. In each cohort, the number of dose-limiting toxicities (DLTs) were observed. Dose escalation rules were the same as those provided by Storer 1989.
The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR).
Time frame: Day 90
The response rate was quantified by examination by an experienced head and neck surgeon and classified as follows: significant response (SR) was one where the lesion had greater than 75% resolution, partial response (PR) was one in which the lesion was reduced in size by at least 25%, and no response (NR) was one where the lesion was reduced by less than 25% in size.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22106236Shafirstein G, Friedman A, Siegel E, Moreno M, Baumler W, Fan CY, Morehead K, Vural E, Stack BC Jr, Suen JY. Using 5-aminolevulinic acid and pulsed dye laser for photodynamic treatment of oral leukoplakia. Arch Otolaryngol Head Neck Surg. 2011 Nov;137(11):1117-23. doi: 10.1001/archoto.2011.178.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gal Shafirstein, PhD principal investigator
University of Arkansas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PDL-585, ScleroPLUS laser, 5-Aminolevulinic Acid (Levulan KerastickTM) and Fluorescence Diagnosis Imaging in people with Leukoplakia and Erythroplakia, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: Day 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00571974, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2015.