Clinical trial NCT01006096: Erlotinib for Treatment of Psoriasis
Official title: Phase II Randomized, Double-blind, Placebo-controlled, Two-arm Study to Evaluate the Safety and Efficacy of Erlotinib in the Treatment of Moderate to Severe Psoriasis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Psoriasis
Keywords: Psoriasis
double-blind
randomized
placebo-controlled
erlotinib
efficacy
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: OSI Pharmaceuticals
First posted: 2009-11-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether erlotinib is effective in the treatment of psoriasis.

Detailed description: Psoriasis vulgaris is a disease that affects 25 million people in North America and Europe. It often presents in late adolescence and usually persists for life. Current therapies target specific immune molecules that are implicated in the cause of this disease. For example, biologic agents that are used in severe psoriasis are aimed at inflammatory mediators. These therapies have been proven to be effective but also have their limitations.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of moderate to severe psoriasis
* Must have documented moderate to severe psoriasis by the Physician's Global Assessment (PGA) and the Psoriasis Area Severity Index (PASI)
* Must be able to swallow tablets
* Must be able to provide written informed consent
* Subjects with reproductive potential (menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study and thirty days after discontinuation of study drug. Women of childbearing potential must provide negative pregnancy test (serum or urine) within 14 days prior to randomization.

Exclusion Criteria:

* Use of concurrent agents/therapies for psoriasis
* Bilirubin \> 3 X ≥ ULN or moderate to severe hepatic impairment
* Pregnant or breast-feeding females
* Subjects currently receiving other anticancer treatments
* Subjects currently receiving other biologic treatments
* Subjects currently receiving blood thinners (warfarin or heparin)
* Subjects who currently smoke
* Subjects with other skin disease which in the opinion of the investigator, would inhibit the ability to use the PGA and PASI evaluation methods

Primary outcomes:
measure: To determine efficacy of erlotinib in treatment of moderate to severe psoriasis measured by the Psoriasis Area and Severity Index (PASI) and the Physician's Global Assessment (PGA).
timeFrame: week 4, 8, 12, 16, and 24
Secondary outcomes:
measure: To determine the rate of dose reduction or interruption as a result of adverse events.
timeFrame: week 4, 8, 12, 16, and 24
measure: To determine quality of life using the Dermatology Life Quality Index (DLQI).
timeFrame: week 4, 8, 12, 16, and 24
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine Department of Dermatology
state: Illinois
Study officials:
affiliation: Northwestern University
name: Anne E Laumann, MBChB, MRCP (UK)
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007 Feb 22;445(7130):866-73. doi: 10.1038/nature05663.
citation: Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. doi: 10.1056/NEJMoa050753.
citation: Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006 Oct;6(10):803-12. doi: 10.1038/nrc1970.
citation: Wierzbicka E, Tourani JM, Guillet G. Improvement of psoriasis and cutaneous side-effects during tyrosine kinase inhibitor therapy for renal metastatic adenocarcinoma. A role for epidermal growth factor receptor (EGFR) inhibitors in psoriasis? Br J Dermatol. 2006 Jul;155(1):213-4. doi: 10.1111/j.1365-2133.2006.07299.x. No abstract available.
citation: Ben-Bassat H, Vardi DV, Gazit A, Klaus SN, Chaouat M, Hartzstark Z, Levitzki A. Tyrphostins suppress the growth of psoriatic keratinocytes. Exp Dermatol. 1995 Apr;4(2):82-8. doi: 10.1111/j.1600-0625.1995.tb00227.x.
citation: Powell TJ, Ben-Bassat H, Klein BY, Chen H, Shenoy N, McCollough J, Narog B, Gazit A, Harzstark Z, Chaouat M, Levitzki R, Tang C, McMahon J, Shawver L, Levitzki A. Growth inhibition of psoriatic keratinocytes by quinazoline tyrosine kinase inhibitors. Br J Dermatol. 1999 Nov;141(5):802-10. doi: 10.1046/j.1365-2133.1999.03152.x.
citation: Ben-Bassat H, Klein BY. Inhibitors of tyrosine kinases in the treatment of psoriasis. Curr Pharm Des. 2000 Jun;6(9):933-42. doi: 10.2174/1381612003400182.
citation: Ben-Bassat H, Levitzki A. Inhibitors of tyrosine kinases in the treatment of psoriasis. Isr Med Assoc J. 2000 Jul;2 Suppl:69-73. No abstract available.
citation: Halin C, Fahrngruber H, Meingassner JG, Bold G, Littlewood-Evans A, Stuetz A, Detmar M. Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Am J Pathol. 2008 Jul;173(1):265-77. doi: 10.2353/ajpath.2008.071074. Epub 2008 Jun 5.
citation: Forsberg S, Ostman A, Rollman O. Regeneration of human epidermis on acellular dermis is impeded by small-molecule inhibitors of EGF receptor tyrosine kinase. Arch Dermatol Res. 2008 Oct;300(9):505-16. doi: 10.1007/s00403-008-0853-2. Epub 2008 Apr 30.
citation: Neyns B, Meert V, Vandenbroucke F. Cetuximab treatment in a patient with metastatic colorectal cancer and psoriasis. Curr Oncol. 2008 Aug;15(4):196-7. doi: 10.3747/co.v15i4.228.
citation: Trivin F, Boucher E, Raoul JL. Complete sustained regression of extensive psoriasis with cetuximab combination chemotherapy. Acta Oncol. 2004;43(6):592-3. doi: 10.1080/02841860410020211. No abstract available.