Efficacy of AFL-assisted PDT in Microinvasive Squamous Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02666534

Recruitment Status : Completed

First Posted : January 28, 2016

Last Update Posted : January 28, 2016

Sponsor:

Information provided by (Responsible Party):

Song Ki-Hoon, Dong-A University

Study Description

Brief Summary:

Surgical excision is the standard treatment for cutaneous SCC. However, many patients diagnosed with SCC are elderly and ineligible for surgery. Ablative fractional laser- assisted photodynamic therapy (AFL-PDT) offered a higher efficacy than conventional Methylaminolevulinate (MAL)-PDT.

Condition or disease	Intervention/treatment	Phase
Microinvasive Squamous Cell Carcinoma	Drug: lidocaine-prilocaine 5% cream application Device: 2940-nm Er:YAG AFL pretreatment Drug: methyl-aminolevulinate application Device: Illuminating using red light-emitting diode lamps	Phase 1

Detailed Description:

Squamous cell carcinoma (SCC) lesions are potentially metastatic and can be life threatening. Hence, surgical excision is the standard treatment for cutaneous SCC. However, some patients are ineligible for surgery because of their poor general health, concomitant anticoagulant or immunosuppressive therapies, or allergy to local anesthetics.

Photodynamic therapy (PDT) with methylaminolevulinate (MAL) is an innovative treatment modality that has been approved in Europe for the treatment of actinic keratosis, basal cell carcinoma, and Bowen's disease. However, currently, there is insufficient evidence to support the routine use of topical PDT for SCC.

Ablative fractional laser (AFL) ablates the epidermis and dermis without significant thermal injury, creating microscopic ablation zones in the portion of the skin that the laser is applied to. Our previous studies showed that AFL-primed MAL-PDT (AFL-PDT) offered a higher efficacy than conventional MAL-PDT in the treatment of many other diseases, such as actinic keratosis, actinic cheilitis, and Bowen's disease.

Investigators recruited Korean patients with microinvasive SCC and compared the efficacy, recurrence rate, and cosmetic outcomes of AFL-PDT with those of standard MAL-PDT.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	45 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	Double (Participant, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomised Trial Comparing Methyl Aminolaevulinate Photodynamic Therapy With and Without Ablative Fractional Laser Treatment in Patients With Microinvasive Squamous Cell Carcinoma: Results From a 24-month Follow-up
Study Start Date :	January 2012
Actual Primary Completion Date :	December 2015
Actual Study Completion Date :	December 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Methyl aminolevulinate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: AFL-PDT Forty-five Korean patients were enrolled in this study. Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT (21 patients) or MAL-PDT (24 patients)	Drug: lidocaine-prilocaine 5% cream application The lesions were then cleansed with saline gauze, and a lidocaine-prilocaine 5% cream (EMLA®; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area for 30 min under occlusion Device: 2940-nm Er:YAG AFL pretreatment After the anesthetic cream was removed, AFL was performed using a 2940-nm Er:YAG AFL (Joule; Sciton, Inc., Palo Alto, CA, USA) with a 500 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse Drug: methyl-aminolevulinate application Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light. Device: Illuminating using red light-emitting diode lamps Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.
Active Comparator: MAL-PDT Forty-five Korean patients were enrolled in this study. Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT (21 patients) or MAL-PDT (24 patients)	Drug: methyl-aminolevulinate application Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light. Device: Illuminating using red light-emitting diode lamps Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.

Arm

Intervention/treatment

Experimental: AFL-PDT

Forty-five Korean patients were enrolled in this study. Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT (21 patients) or MAL-PDT (24 patients)

Drug: lidocaine-prilocaine 5% cream application

The lesions were then cleansed with saline gauze, and a lidocaine-prilocaine 5% cream (EMLA®; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area for 30 min under occlusion

Device: 2940-nm Er:YAG AFL pretreatment

After the anesthetic cream was removed, AFL was performed using a 2940-nm Er:YAG AFL (Joule; Sciton, Inc., Palo Alto, CA, USA) with a 500 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse

Drug: methyl-aminolevulinate application

Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light.

Device: Illuminating using red light-emitting diode lamps

Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.

Active Comparator: MAL-PDT

Drug: methyl-aminolevulinate application

Device: Illuminating using red light-emitting diode lamps

Outcome Measures

Primary Outcome Measures :

Difference of short-term complete response (CR) rate between AFL-PDT and MAL-PDT [ Time Frame: Short-term CR rate was evaluated at 3 months ]
The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)
Difference of long-term complete response (CR) rate between AFL-PDT and MAL-PDT [ Time Frame: Long-term CR rate was evaluated at 24 months ]
The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)
Difference of recurrence rate at 24 months [ Time Frame: Recurrent rate was evaluated at 24months ]
In all cases of complete response, the patients were reviewed at 24 months to check for recurrence. Post-therapy punch biopsies were performed when there was doubt concerning incomplete-response and clinical recurrence

Secondary Outcome Measures :

Difference of the cosmetic outcome between AFL-PDT and MAL-PDT [ Time Frame: Cosmetic outcome was assessed by each investigator for all lesions that achieved a complete response at 24 months ]
The overall cosmetic outcome was assessed by each investigator for all lesions that achieved complete response at 24 months, and was graded using a 4-point scale: excellent (only slight occurrence of redness or change in pigmentation), good (moderate redness or change in pigmentation), fair (slight to moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration)

Other Outcome Measures:

Differences of Adverse events(erythema, burning sensation, swelling, bleeding) between AFL-PDT and MAL-PDT [ Time Frame: Within 24 months after each treatment ]
Adverse events reported by the patients were noted at each follow-up visit, including severity, duration, and need for additional therapy. All events due to PDT were described as phototoxic reactions(e.g erythema, burning sensation, swelling, bleeding)

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	65 Years to 89 Years (Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Patients aged 18 years or more who had previously untreated microinvasive SCC, providing they satisfied both of the following conditions:
- tumor invasion into the papillary dermis (Clark level II) according to a biopsy specimen and
- difficulty in surgical excision because of health problems (bleeding tendency or cardiac problems)

Exclusion Criteria:

pregnancy or lactation
active systemic infectious disease
other inflammatory, infectious, or neoplastic skin diseases in the treated area
allergy to MAL,other topical photosensitizers, or excipients of the cream
history of photosensitivity
use of immunosuppressive or photosensitizing drugs
participation in any other investigational study in the preceding 30 days
history or indicators of poor compliance
Histological findings of acantholysis, desmoplasia, perineural or lymphovascular invasion, and echographic features of regional lymph node metastasis were the disease-specific exclusion criteria

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02666534

Locations

Layout table for location information

Korea, Republic of
Dong-A University
Busan, Dong dae sin-dong, Seo-gu, Korea, Republic of, 602-715

Sponsors and Collaborators

Dong-A University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Choi SH, Kim KH, Song KH. Effect of Methyl Aminolevulinate Photodynamic Therapy With and Without Ablative Fractional Laser Treatment in Patients With Microinvasive Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Dermatol. 2017 Mar 1;153(3):289-295. doi: 10.1001/jamadermatol.2016.4463.

Layout table for additonal information

Responsible Party:	Song Ki-Hoon, Associate professor, Dong-A University
ClinicalTrials.gov Identifier:	NCT02666534
Other Study ID Numbers:	DAUderma-05
First Posted:	January 28, 2016 Key Record Dates
Last Update Posted:	January 28, 2016
Last Verified:	January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Song Ki-Hoon, Dong-A University:


Ablative fractional laser microinvasive squamous cell carcinoma photodynamic therapy

Additional relevant MeSH terms:

Layout table for MeSH terms

Carcinoma Carcinoma, Squamous Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Lidocaine Prilocaine Lidocaine, Prilocaine Drug Combination Aminolevulinic Acid Methyl 5-aminolevulinate Anesthetics, Local Anesthetics	Central Nervous System Depressants Physiological Effects of Drugs Sensory System Agents Peripheral Nervous System Agents Anti-Arrhythmia Agents Voltage-Gated Sodium Channel Blockers Sodium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Photosensitizing Agents Dermatologic Agents Anesthetics, Combined

To Top