Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip

This study has been completed.
Sponsor:
Collaborator:
DUSA Pharmaceuticals, Inc.
Information provided by:
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT00868088
First received: March 23, 2009
Last updated: July 5, 2011
Last verified: July 2011
  Purpose

Our study is designed to evaluate the efficacy of photodynamic therapy (PDT) for treatment of actinic cheilitis (AC) and as an adjunct to Mohs surgery for squamous cell carcinoma (SCC) on the lips. This study will utilize an FDA approved PDT modality (DUSA, Inc., Wilmington, MA 01887) using topical 5-amino-levulinic acid (ALA) for photosensitization followed by exposure to a Blu-U light source emitting 405-420nm wavelength light.


Condition Intervention Phase
Actinic Cheilitis
Squamous Cell Carcinoma In-situ (SCC-is)
Squamous Cell Carcinoma (SCC)
Photodynamic Therapy (PDT)
Mohs Surgery
Procedure: PDT prior to Mohs surgery
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Clinical Trial of ALA Photodynamic Therapy for Treatment of Actinic Cheilitis in Patients With Squamous Cell Carcinoma of the Lip.

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • To determine whether pre-operative treatment of the lips with ALA PDT can reduce the size of post-surgical defects (scars) in patients with AC and lip SCC. [ Time Frame: at time of Mohs ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine whether ALA PDT applied to the lips can effectively clear actinic cheilitis (AC) and SCC in-situ (SCC-is) of the lip. [ Time Frame: at time of Mohs. ] [ Designated as safety issue: No ]
  • To assess the tolerability of ALA PDT for treatment of AC and SCC-is of the lips [ Time Frame: at time of PDT and Mohs ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 34
Study Start Date: July 2009
Study Completion Date: September 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ALA + PDT
Topical ALA will be applied to the entire lip surface and allowed to incubate for 60 minutes plus or minus 30 minutes. Blue light at a wavelength of 405-420 nm will be used for treatment at a dose of 1000 seconds.
Procedure: PDT prior to Mohs surgery

Day 1: Screening and consent for this study. If eligible, a scouting biopsy will be obtained at 1 cm from the clinical border of the SCC for confirmation of AC.

7-14 Days after consultation: PDT to all subjects in the study. If during treatment a subject requests to discontinue due to pain the treatment will be terminated.

3-5 weeks after consultation: return for assessment. At this visit, the assigned treatment may be repeated if the treatment site is adequately healed. Re-treatment will only occur if there is persistent actinic damage.

6-8 weeks after consultation: Mohs surgery will be performed as per routine. Following tumor removal a scouting biopsy will be taken at a site 1 cm from the wound site created by SCC removal. The current waiting time for non-urgent surgery is 8 weeks. Standard care is not being altered for subjects in the study, other then their receiving the PDT intervention.

Photographs may be taken at each subject visit.

Placebo Comparator: placebo + PDT
Topical placebo will be applied to the entire lip surface and allowed to incubate for 60 minutes plus or minus 30 minutes. Blue light at a wavelength of 405-420 nm will be used for treatment at a dose of 1000 seconds.
Procedure: PDT prior to Mohs surgery

Day 1: Screening and consent for this study. If eligible, a scouting biopsy will be obtained at 1 cm from the clinical border of the SCC for confirmation of AC.

7-14 Days after consultation: PDT to all subjects in the study. If during treatment a subject requests to discontinue due to pain the treatment will be terminated.

3-5 weeks after consultation: return for assessment. At this visit, the assigned treatment may be repeated if the treatment site is adequately healed. Re-treatment will only occur if there is persistent actinic damage.

6-8 weeks after consultation: Mohs surgery will be performed as per routine. Following tumor removal a scouting biopsy will be taken at a site 1 cm from the wound site created by SCC removal. The current waiting time for non-urgent surgery is 8 weeks. Standard care is not being altered for subjects in the study, other then their receiving the PDT intervention.

Photographs may be taken at each subject visit.


Detailed Description:

BACKGROUND:

SCC of the lip is commonly surrounded by extensive AC, which may affect part or all of the lip vermillion. While Mohs surgical technique with complete margin control is the preferred treatment for SCC at critical locations such as the lip, this technique is complicated by surrounding AC. AC and SCC in situ at the tumor edge make it difficult to achieve margins clear of dysplasia and as a result extra tissue beyond the invasive SCC often needs to be excised to ensure that the entire tumor is removed.

Non-surgical treatments when used alone to treat SCC give lower cure rates than surgical removal, and thus are not recommended as they place the subject at risk for recurrence and metastatic disease. Although one study reported high SCC clearance rates with PDT alone (24/25 SCCs histologically cleared), recurrence of 2 SCCs occurred and a metastasis to a LN was seen in one patient. (Kubler et al.)

Given that PDT has been shown to have significant efficacy for actinic keratoses and actinic cheilitis but is inadequate as primary treatment of lip SCC, we propose that PDT may be a useful adjunct to surgical resection, allowing for less extensive surgery after the dysplasia is addressed with PDT and potentially a lower recurrence rate. Although imiquimod and 5-FU are also used to treat cutaneous dysplasia, many favor PDT treatment due to its greater tolerability, shorter healing time, and more predictable host response.

There is significant data on the efficacy of PDT for treatment of actinic keratoses (AKs) and PDT is now FDA approved for treatment of AKs. (Piacquadio et al). Data on PDT for treatment of AC is much more limited, but small studies and case reports do indicate successful treatment of AC with regimens utilizing either topical 5-aminolevulinic acid (5-ALA), or a similar compound, methylaminopentanoate (MAL). The largest study with 5-ALA reports complete clinical clearance in 13/19 patients treated with 1 to 3 treatments of ALA plus Pulsed-dye laser (Alexiades). Sotiriou et al report that with two PDT treatments 8/10 patients had complete clinical and histologic clearance (Sotiriou). Case reports indicate similar success (Kodama; Stender). Efficacy has also been shown with MAL PDT. One study found that with two sessions of MAL + red light PDT complete histologic/ clinical clearance was seen in 7/15 cases of AC and partial clearance was seen in an additional 7/15 (Berking et al). Smaller studies and case reports have shown even higher response rates without clinical recurrence during short-term follow-up (Rossi et al; Hauschild et al). We have chosen 5-ALA plus blue light for PDT treatment in this study because it is FDA approved for treatment of AKs and ALA is available in the United States.

Specific Aims:

  1. To determine whether pre-operative treatment of the lips with ALA PDT can reduce the size of post-surgical defects (scars) in subjects with AC and lip SCC
  2. To determine whether ALA PDT applied to the lips can effectively clear actinic cheilitis (AC) and SCC in-situ (SCC-is) of the lip.
  3. To assess the tolerability of ALA PDT for treatment of AC and SCC-is of the lips
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy proven squamous cell carcinoma of the lip
  • Greater than 50% of lip affected by actinic cheilitis by physical exam at time of initial evaluation.
  • Patients > 18 years of age
  • Patients must be able to provide informed consent

Exclusion Criteria:

  • Patients with history of photosensitivity
  • Patients with medical conditions associated with photosensitivity, such as cutaneous porphyria or a collagen vascular disease
  • Patients taking medications known to cause photosensitivity (tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, and fluoroquinolones)
  • Patients with hypersensitivity to porphyrins.
  • Women who are pregnant or nursing
  • No exclusion based on gender or race
  • Patients who have received anti-neoplastic treatment such as imiquimod or 5-FU to the lips within 30 days of enrolling in this study.
  • Patients simultaneously participating in another research study for management of SCC or actinic cheilitis
  • Subjects that plan to use other forms of AC treatment prior to Mohs.
  • Subjects that have an SCC requiring urgent (and sooner) Mohs surgery, including those tumors that are large (> 2cm or at the discretion of the Principle Investigator) and those subjects that are pregnant or have palpable lymph nodes.
  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: NCT00868088

Locations
United States, Massachusetts
Tufts Medical Center, Department of Dermatology
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
DUSA Pharmaceuticals, Inc.
Investigators
Principal Investigator: Gary Rogers, M.D. Tufts Medical Center, Department of Dermatology
  More Information

Additional Information:
Publications:

Responsible Party: Gary Rogers, MD, Tufts Medical Center Department of Dermatology
ClinicalTrials.gov Identifier: NCT00868088     History of Changes
Other Study ID Numbers: PDT for Lip
Study First Received: March 23, 2009
Last Updated: July 5, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Tufts Medical Center:
AC
SCC
SCC-is
PDT
Mohs

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma
Carcinoma in Situ
Cheilitis
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Lip Diseases
Mouth Diseases
Stomatognathic Diseases

ClinicalTrials.gov processed this record on September 30, 2014