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

Brief Title

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

Official Title

A Clinical Trial of ALA Photodynamic Therapy for Treatment of Actinic Cheilitis in Patients With Squamous Cell Carcinoma of the Lip.

Brief Summary

      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.
    

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
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

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.

Secondary Outcome

 To determine whether ALA PDT applied to the lips can effectively clear actinic cheilitis (AC) and SCC in-situ (SCC-is) of the lip.

Condition

Actinic Cheilitis

Intervention

PDT prior to Mohs surgery

Study Arms / Comparison Groups

 ALA + PDT
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

34

Start Date

July 2009

Completion Date

September 2010

Primary Completion Date

July 2010

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Gary Rogers, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00868088

Organization ID

PDT for Lip



Study Sponsor

Tufts Medical Center

Collaborators

 DUSA Pharmaceuticals, Inc.

Study Sponsor

Gary Rogers, M.D., Principal Investigator, Tufts Medical Center, Department of Dermatology


Verification Date

July 2011