A New Light-Emitting, Fabric-Based Device for Photodynamic Therapy of Actinic Keratosis: Protocol for a Randomized, Controlled, Multicenter, Intra-Individual, Phase II Noninferiority Study (the Phosistos Study)

Anne-Sophie Vignion-Dewalle, Henry Abi Rached, Elise Thecua, Fabienne Lecomte, Pascal Deleporte, Hélène Béhal, Theresa Hommel, Alain Duhamel, Rolf-Markus Szeimies, Laurent Mortier, Serge Mordon, Anne-Sophie Vignion-Dewalle, Henry Abi Rached, Elise Thecua, Fabienne Lecomte, Pascal Deleporte, Hélène Béhal, Theresa Hommel, Alain Duhamel, Rolf-Markus Szeimies, Laurent Mortier, Serge Mordon

Abstract

Background: Actinic keratosis (AK) is a common early in situ skin carcinoma caused by long-term sun exposure and usually develops on sun-exposed skin areas. Left untreated, AK may progress to squamous cell carcinoma. To prevent such risk, most clinicians routinely treat AK. Therapy options for AK include cryotherapy, topical treatments, curettage, excision surgery, and photodynamic therapy (PDT).

Objective: The aim of this study is to assess the noninferiority, in terms of efficacy at 3 months, of a PDT protocol involving a new light-emitting device (PDT using the Phosistos protocol [P-PDT]) compared with the conventional protocol (PDT using the conventional protocol [C-PDT]) in the treatment of AK.

Methods: In this randomized, controlled, multicenter, intra-individual, phase II noninferiority clinical study, subjects with AK of the forehead and scalp are treated with P-PDT on one area and with C-PDT on the contralateral area. In both areas, lesions are prepared and methyl aminolevulinate (MAL) is applied. Thirty minutes after MAL application, the P-PDT area is exposed to red light at low irradiance (1.3 mW/cm2) for 2.5 hours so that a light dose of 12 J/cm2 is achieved. In the control area (C-PDT area), a 37 J/cm2 red light irradiation is performed 3 hours after MAL application. Recurrent AK at 3 months is retreated. The primary end point is the lesion complete response rate at 3 months. Secondary end points include pain scores at 1 day, local tolerance at 7 days, lesion complete response rate at 6 months, cosmetic outcome at 3 and 6 months, and patient-reported quality of life and satisfaction throughout the study. A total of 45 patients needs to be recruited.

Results: Clinical investigations are complete: 46 patients were treated with P-PDT on one area (n=285 AK) and with C-PDT on the contralateral area (n=285 AK). Data analysis is ongoing, and statistical results will be available in the first half of 2019.

Conclusions: In case of noninferiority in efficacy and superiority in tolerability of P-PDT compared with C-PDT, P-PDT could become the treatment of choice for AK.

Trial registration: ClinicalTrials.gov NCT03076892; https://ichgcp.net/clinical-trials-registry/NCT03076892 (Archived by WebCite at http://www.webcitation.org/779qqVKek).

International registered report identifier (irrid): DERR1-10.2196/12990.

Keywords: Aktilite CL 128 lamp; actinic keratosis; light-emitting fabric; photodynamic therapy.

Conflict of interest statement

Conflicts of Interest: SM, ASVD, HAR, ET, FL, CV, PD, HB, DK, TH, and AD declare that they have no competing interest. RMS is the vice president of EURO-PDT. He has been a member of advisory boards for Almirall, Biofrontera, Galderma, ISDIN, LEO Pharma, photonamic, and Pierre-Fabre and has received speakers’ honoraria from the aforementioned companies. LM has been a member of advisory boards for BMS, Roche, GSK, Novartis, LEO Pharma, and MSD. He has received travel grants for attending congresses from BMS, Roche, GSK, Novartis, and LEO Pharma. He has been the principal investigator of clinical trials performed for BMS, Roche, GSK, Novartis, LEO Pharma, and MSD.

©Anne-Sophie Vignion-Dewalle, Henry Abi Rached, Elise Thecua, Fabienne Lecomte, Pascal Deleporte, Hélène Béhal, Theresa Hommel, Alain Duhamel, Rolf-Markus Szeimies, Laurent Mortier, Serge Mordon. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 26.04.2019.

Figures

Figure 1
Figure 1
The light-emitting, fabric-based device involved in photodynamic therapy using the phosistos protocol: 635-nm red light is emitted at 1.3 mW/cm2 by a fiber optic–based fabric that lines the inside of a cap.
Figure 2
Figure 2
Study flow diagram. V1: first treatment visit; V2: first evaluation visit; V3: second treatment visit; V3bis in case of recurrent actinic keratosis: second treatment visit; V4: third treatment visit.

References

    1. Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):23–4. doi: 10.1067/mjd.2000.103339.
    1. Stockfleth E, Ferrandiz C, Grob J, Leigh I, Pehamberger H, Kerl H, European Skin Academy Development of a treatment algorithm for actinic keratoses: a European Consensus. Eur J Dermatol. 2008;18(6):651–9. doi: 10.1684/ejd.2008.0514.
    1. Plaetzer K, Krammer B, Berlanda J, Berr F, Kiesslich T. Photophysics and photochemistry of photodynamic therapy: fundamental aspects. Lasers Med Sci. 2009 Mar;24(2):259–68. doi: 10.1007/s10103-008-0539-1.
    1. Braathen L, Szeimies R, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, Roelandts R, Wennberg A, Morton C, International Society for Photodynamic Therapy in Dermatology Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. 2007 Jan;56(1):125–43. doi: 10.1016/j.jaad.2006.06.006.
    1. Ericson M, Wennberg A, Larkö O. Review of photodynamic therapy in actinic keratosis and basal cell carcinoma. Ther Clin Risk Manag. 2008 Feb;4(1):1–9. doi: 10.2147/TCRM.S1769.
    1. Morton C, McKenna K, Rhodes L, British Association of Dermatologists Therapy Guidelines and Audit Subcommittee and the British Photodermatology Group Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008 Dec;159(6):1245–66. doi: 10.1111/j.1365-2133.2008.08882.x.
    1. Morton C, Szeimies R, Sidoroff A, Wennberg A, Basset-Seguin N, Calzavara-Pinton P, Gilaberte Y, Hofbauer G, Hunger R, Karrer S, Lehmann P, Piaserico S, Ulrich C, Braathen L, European Dermatology Forum European Dermatology Forum Guidelines on topical photodynamic therapy. Eur J Dermatol. 2015;25(4):296–311. doi: 10.1684/ejd.2015.2570.
    1. Wiegell SR. Update on photodynamic treatment for actinic keratosis. Curr Probl Dermatol. 2015;46:122–8. doi: 10.1159/000366548.
    1. Morton C, Campbell S, Gupta G, Keohane S, Lear J, Zaki I, Walton S, Kerrouche N, Thomas G, Soto P, AKtion Investigators Intraindividual, right-left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study. Br J Dermatol. 2006 Nov;155(5):1029–36. doi: 10.1111/j.1365-2133.2006.07470.x.
    1. Pariser D, Loss R, Jarratt M, Abramovits W, Spencer J, Geronemus R, Bailin P, Bruce S. Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: a randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2008 Oct;59(4):569–76. doi: 10.1016/j.jaad.2008.05.031.
    1. Szeimies R, Matheson R, Davis S, Bhatia A, Frambach Y, Klövekorn W, Fesq H, Berking C, Reifenberger J, Thaçi D. Topical methyl aminolevulinate photodynamic therapy using red light-emitting diode light for multiple actinic keratoses: a randomized study. Dermatol Surg. 2009 Apr;35(4):586–92. doi: 10.1111/j.1524-4725.2009.01096.x.
    1. Tyrrell J, Campbell S, Curnow A. The effect of air cooling pain relief on protoporphyrin IX photobleaching and clinical efficacy during dermatological photodynamic therapy. J Photochem Photobiol B. 2011 Apr 4;103(1):1–7. doi: 10.1016/j.jphotobiol.2010.12.011.
    1. Stangeland K, Kroon S. Cold air analgesia as pain reduction during photodynamic therapy of actinic keratoses. J Eur Acad Dermatol Venereol. 2012 Jul;26(7):849–54. doi: 10.1111/j.1468-3083.2011.04167.x.
    1. Wiegell S, Haedersdal M, Philipsen P, Eriksen P, Enk C, Wulf HC. Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study. Br J Dermatol. 2008 Apr;158(4):740–6. doi: 10.1111/j.1365-2133.2008.08450.x.
    1. Wiegell S, Haedersdal M, Eriksen P, Wulf HC. Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial. Br J Dermatol. 2009 Jun;160(6):1308–14. doi: 10.1111/j.1365-2133.2009.09119.x.
    1. Wiegell S, Fabricius S, Stender I, Berne B, Kroon S, Andersen B, Mørk C, Sandberg C, Jemec G, Mogensen M, Brocks KM, Philipsen PA, Heydenreich J, Haedersdal M, Wulf HC. A randomized, multicentre study of directed daylight exposure times of 1½ vs 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp. Br J Dermatol. 2011 May;164(5):1083–90. doi: 10.1111/j.1365-2133.2011.10209.x.
    1. Wiegell S, Fabricius S, Gniadecka M, Stender I, Berne B, Kroon S, Andersen B, Mørk C, Sandberg C, Ibler KS, Jemec GB, Brocks KM, Philipsen PA, Heydenreich J, Hædersdal M, Wulf HC. Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study. Br J Dermatol. 2012 Jun;166(6):1327–32. doi: 10.1111/j.1365-2133.2012.10833.x.
    1. Wiegell S, Wulf H, Szeimies R, Basset-Seguin N, Bissonnette R, Gerritsen M, Gilaberte Y, Calzavara-Pinton P, Morton C, Sidoroff A, Braathen LR. Daylight photodynamic therapy for actinic keratosis: an international consensus: International Society for Photodynamic Therapy in Dermatology. J Eur Acad Dermatol Venereol. 2012 Jun;26(6):673–9. doi: 10.1111/j.1468-3083.2011.04386.x.
    1. Wiegell S, Fabricius S, Heydenreich J, Enk C, Rosso S, Bäumler W, Baldursson B, Wulf HC. Weather conditions and daylight-mediated photodynamic therapy: protoporphyrin IX-weighted daylight doses measured in six geographical locations. Br J Dermatol. 2013 Jan;168(1):186–91. doi: 10.1111/j.1365-2133.2012.11200.x.
    1. Lecomte F, Vignion-Dewalle A, Vicentini C, Thecua E, Deleporte P, Duhamel A, Mordon S, Mortier L. A phase II study evaluating the non-inferiority of a photodynamic therapy protocol involving the Flexitheralight device compared to the conventional protocol (the FLEXITHERALIGHT study) JMIR Res Protoc. 2019 doi: 10.2196/preprints.11530.
    1. Vicentini C, Vignion-Dewalle AS, Thecua E, Lecomte F, Maire C, Deleporte P, Béhal H, Kerob D, Duhamel A, Mordon S, Mortier L. Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the noninferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp. Br J Dermatol. 2019 Apr;180(4):765–73. doi: 10.1111/bjd.17350.
    1. Vignion-Dewalle A, Baert G, Thecua E, Lecomte F, Vicentini C, Abi-Rached H, Mortier L, Mordon S. Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months? Lasers Surg Med. 2018 Dec;50(5):576–89. doi: 10.1002/lsm.22827.
    1. Olsen E, Abernethy M, Kulp-Shorten C, Callen J, Glazer S, Huntley A, McCray M, Monroe A, Tschen E, Wolf J. A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. J Am Acad Dermatol. 1991 May;24(5 Pt 1):738–43. doi: 10.1016/0190-9622(91)70113-G.
    1. Wiegell S, Skiveren J, Philipsen P, Wulf HC. Pain during photodynamic therapy is associated with protoporphyrin IX fluorescence and fluence rate. Br J Dermatol. 2008 Apr;158(4):727–33. doi: 10.1111/j.1365-2133.2008.08451.x.
    1. Arits A, van de Weert MM, Nelemans P, Kelleners-Smeets NW. Pain during topical photodynamic therapy: uncomfortable and unpredictable. J Eur Acad Dermatol Venereol. 2010 Dec;24(12):1452–7. doi: 10.1111/j.1468-3083.2010.03670.x.
    1. Serra-Guillen C, Hueso L, Nagore E, Vila M, Llombart B, Requena Caballero C, Botella-Estrada R, Sanmartin O, Alfaro-Rubio A, Guillen C. Comparative study between cold air analgesia and supraorbital and supratrochlear nerve block for the management of pain during photodynamic therapy for actinic keratoses of the frontotemporal zone. Br J Dermatol. 2009 Aug;161(2):353–6. doi: 10.1111/j.1365-2133.2009.09184.x.
    1. Rubel D, Spelman L, Murrell D, See J, Hewitt D, Foley P, Bosc C, Kerob D, Kerrouche N, Wulf HC, Shumack S. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial. Br J Dermatol. 2014 Nov;171(5):1164–71. doi: 10.1111/bjd.13138.
    1. Lerche C, Heerfordt I, Heydenreich J, Wulf HC. Alternatives to outdoor daylight illumination for photodynamic therapy—use of greenhouses and artificial light sources. Int J Mol Sci. 2016 Feb 29;17(3):309. doi: 10.3390/ijms17030309.
    1. Ibbotson S, Ferguson J. Ambulatory photodynamic therapy using low irradiance inorganic light-emitting diodes for the treatment of non-melanoma skin cancer: an open study. Photodermatol Photoimmunol Photomed. 2012 Oct;28(5):235–9. doi: 10.1111/j.1600-0781.2012.00681.x.
    1. Apalla Z, Sotiriou E, Panagiotidou D, Lefaki I, Goussi C, Ioannides D. The impact of different fluence rates on pain and clinical outcome in patients with actinic keratoses treated with photodynamic therapy. Photodermatol Photoimmunol Photomed. 2011 Aug;27(4):181–5. doi: 10.1111/j.1600-0781.2011.00595.x.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj