Histological Characterization and Differentiation of Rash From Other Epidermal Growth Factor Receptor (EGFR) Inhibitors

Skin Rash Clinical Trial

Official title:

Histological Characterization and Differentiation of Rash From Other EGFR Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00709878
• Other study ID #: GSK-Lapatinib
• Status: Completed
• Phase: N/A
• First received: July 1, 2008
• Last updated: February 24, 2015
• Start date: April 2008
• Est. completion date: August 2010

Study information

• Verified date: February 2015
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to characterize the microscopic findings of skin rash associated with the use of chemotherapeutic anticancer agents known as epidermal growth factor inhibitors (EGFRIs).

Description:

Epidermal growth factor (EGF) and its receptor, the EGFR, are known to be key drivers in cellular proliferation and survival. Malignant tumors result from uncontrolled cell proliferation. The use of drugs which target the EGF receptor has offered patients with non-small cell lung cancer, pancreatic cancer, head and neck cancer, and colorectal cancer additional targeted anti-cancer therapy in addition to their chemotherapeutic regimens. As a result of increased use of these EGFR inhibitors, adverse events have emerged involving the skin, hair, nails and eyes. While the EGFR inhibitors block the signal transduction that interfere with cellular proliferation and survival of cancerous cells, they also affect the normal EGF function in the skin (papulopustular rash), hair, and nails. In this study, we seek to histologically characterize the papulopustular rash in patients who have been treated with lapatinib and compare our findings with those associated with three other EGFRIs, cetuximab, erlotinib and panitumumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients treated with lapatinib who developed skin toxicities and were biopsied.

• Patients treated with erlotinib, cetuximab, or panitumumab who have been biopsied for skin rash.

Exclusion Criteria:

• Patients who do not fit above criteria.

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Skin Rash

Intervention

Procedure:
• Skin Biopsy of Skin Rash Secondary to EGFRI Use
Patients who were treated with lapatinib, cetuximab, panitumumab or erlotinib who subsequently developed a skin rash have been biopsied as standard of care. The biopsies will be used for this study.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (24)

Albanell J, Rojo F, Averbuch S, Feyereislova A, Mascaro JM, Herbst R, LoRusso P, Rischin D, Sauleda S, Gee J, Nicholson RI, Baselga J. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol. 2002 Jan 1;20(1):110-24. — View Citation

Busse D, Doughty RS, Ramsey TT, Russell WE, Price JO, Flanagan WM, Shawver LK, Arteaga CL. Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27(KIP1) independent of MAPK activity. J Biol Chem. 2000 Mar 10;275(10):6987-95. — View Citation

Cameron D. Lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer. Clin Adv Hematol Oncol. 2007 Jun;5(6):456-8. — View Citation

El-Abaseri TB, Putta S, Hansen LA. Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. Carcinogenesis. 2006 Feb;27(2):225-31. Epub 2005 Aug 25. — View Citation

Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJ. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature. 1996 Jan 25;379(6563):335-9. — View Citation

Fuchs E, Raghavan S. Getting under the skin of epidermal morphogenesis. Nat Rev Genet. 2002 Mar;3(3):199-209. Review. — View Citation

Gullick WJ. The Type 1 growth factor receptors and their ligands considered as a complex system. Endocr Relat Cancer. 2001 Jun;8(2):75-82. Review. — View Citation

Hauser PJ, Agrawal D, Hackney J, Pledger WJ. STAT3 activation accompanies keratinocyte differentiation. Cell Growth Differ. 1998 Oct;9(10):847-55. — View Citation

Jost M, Kari C, Rodeck U. The EGF receptor - an essential regulator of multiple epidermal functions. Eur J Dermatol. 2000 Oct-Nov;10(7):505-10. Review. — View Citation

Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006 Oct;6(10):803-12. Review. — View Citation

Lorch JH, Klessner J, Park JK, Getsios S, Wu YL, Stack MS, Green KJ. Epidermal growth factor receptor inhibition promotes desmosome assembly and strengthens intercellular adhesion in squamous cell carcinoma cells. J Biol Chem. 2004 Aug 27;279(35):37191-200. Epub 2004 Jun 16. — View Citation

Marmor MD, Skaria KB, Yarden Y. Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):903-13. Review. — View Citation

Mimeault M, Bonenfant D, Batra SK. New advances on the functions of epidermal growth factor receptor and ceramides in skin cell differentiation, disorders and cancers. Skin Pharmacol Physiol. 2004 Jul-Aug;17(4):153-66. Review. — View Citation

Molinari E, De Quatrebarbes J, André T, Aractingi S. Cetuximab-induced acne. Dermatology. 2005;211(4):330-3. — View Citation

Moy B, Goss PE. Lapatinib: current status and future directions in breast cancer. Oncologist. 2006 Nov-Dec;11(10):1047-57. Review. — View Citation

Nardone B, Nicholson K, Newman M, Guitart J, Gerami P, Talarico N, Yang XJ, Rademaker A, West DP, Lacouture ME. Histopathologic and immunohistochemical characterization of rash to human epidermal growth factor receptor 1 (HER1) and HER1/2 inhibitors in ca — View Citation

Nelson MH, Dolder CR. Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors. Ann Pharmacother. 2006 Feb;40(2):261-9. Epub 2006 Jan 17. Review. — View Citation

Pastore S, Mascia F, Mariotti F, Dattilo C, Mariani V, Girolomoni G. ERK1/2 regulates epidermal chemokine expression and skin inflammation. J Immunol. 2005 Apr 15;174(8):5047-56. — View Citation

Pérez-Soler R, Delord JP, Halpern A, Kelly K, Krueger J, Sureda BM, von Pawel J, Temel J, Siena S, Soulières D, Saltz L, Leyden J. HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist. 2005 May;10(5):345-56. Review. — View Citation

Peus D, Hamacher L, Pittelkow MR. EGF-receptor tyrosine kinase inhibition induces keratinocyte growth arrest and terminal differentiation. J Invest Dermatol. 1997 Dec;109(6):751-6. — View Citation

Robert C, Soria JC, Spatz A, Le Cesne A, Malka D, Pautier P, Wechsler J, Lhomme C, Escudier B, Boige V, Armand JP, Le Chevalier T. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005 Jul;6(7):491-500. Review. — View Citation

Rodeck U, Jost M, Kari C, Shih DT, Lavker RM, Ewert DL, Jensen PJ. EGF-R dependent regulation of keratinocyte survival. J Cell Sci. 1997 Jan;110 ( Pt 2):113-21. — View Citation

Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2000 Oct 13;103(2):211-25. Review. — View Citation

Woodworth CD, Michael E, Marker D, Allen S, Smith L, Nees M. Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment. Mol Cancer Ther. 2005 Apr;4(4):650-8. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in Histologic Alterations in Rash Caused by Lapatinib, a Dual HER1/2 Inhibitor (HER1/2i), and the Single HER1 Inhibitors (HER1i) Cetuximab, Erlotinib,and Panitumumab.		6 months	No