Clinical trial NCT00240682: Study of Cetuximab in Squamous Cell Carcinoma of the Skin Expressing EGFR
Official title: Phase II Study of Cetuximab as Monotherapy and First Line Treatment in Patients With Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin Expressing EGFR.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Skin Diseases
Carcinoma, Squamous Cell
Keywords: Carcinoma, Squamous Cell
Skin
cetuximab
epidermal growth factor receptor
Lead sponsor: Centre Hospitalier of Chartres
Sponsor class: OTHER
Collaborators: name: Hospital of Chartres- France
First posted: 2005-10-18
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether cetuximab is effective in the treatment of locally advanced or metastatic squamous cell carcinoma of the skin expressing EGFR.

Detailed description: Patients with locally advanced or metastatic squamous cell carcinoma (SCC) of the skin are often bad responders to conventional chemotherapy included cisplatin.

The investigation of the EGFR expression may allow identifying new molecular targets for novel therapeutic strategies in patients with locally advanced or metastatic SCC of the skin.

Several publications in the literature for primary lesions and one publication for metastatic lesions showed that EGFR was expressed in 80-90% of SCC of the skin. Immunohistochemistry studies performed at the Gustave Roussy Institute confirm these data: they found an over-expression of EGFR in 90% of patients with metastatic disease. These results are in favor of the investigation of cetuximab in patients with locally advanced or metastatic SCC of the skin expressing EGFR.

Cetuximab is a monoclonal antibody targeted against EGFR administered weekly by intravenous route; it may be prescribed as out hospital to patients with locally advanced or metastatic SCC of the skin expressing EGFR.

Due to the low occurrence of locally advanced or metastatic SCC of the skin, a multicenter trial will be required.

Eligibility criteria: Inclusion Criteria:

* Histological SCC of the skin expressing (IHC) moderately or highly the EGFR (++ and +++, on a semi-quantitative scale).
* Locally advanced or metastatic SCC of the skin not suitable for local surgery with documented progression.
* Presence of at least one measurable target lesion by RECIST criteria.
* At least one lesion accessible to biopsies.
* ECOG Performance status \< 2.
* Life expectancy \> 3 months.
* Age \> 18 years.
* Normal hematological (Neutrophils \> 1.5x109 cells/l, platelets \> 100x109 cells/l), hepatic (bilirubin \< 1.5 times the upper limit of the normal range (ULN); alkaline phosphatase and transaminases \< 5 x UNL in case of hepatic metastases or \< 2.5 x UNL in absence of hepatic metastases) and renal (serum creatinine \< 150 micromol/L) functions.
* Written informed consent.
* In case of second tumor,excepted carcinoma of the cervix and adequately treated basal or squamous cell skin carcinoma, the possibility for including a patient may be discussed with the principal investigator.

Exclusion Criteria:

* Prior chemotherapy
* Prior radiotherapy \< 1 month.
* Prior therapy with agent targeting EGFR
* Unstable systemic diseases or active uncontrolled infections.
* Patients (male and female) not using effective contraception if of reproductive potential.
* Females pregnant or lactating. Women of child bearing potential must have a negative serum or urine pregnancy test prior to start each cycle of treatment.

Primary outcomes:
measure: Disease control rate assessed by CT or MRI
timeFrame: 6 weeks
Secondary outcomes:
measure: Safety profile.
timeFrame: during treatment or within 30 days after the final administration with a cut-off date at week 48.
measure: Time to disease progression.
timeFrame: number of days from the start of treatment to the earliest day of progressive disease
measure: Overall survival.
timeFrame: from the first infusion until week 48 or death
measure: Duration of response in responder patients at 6 weeks.
timeFrame: time to disease progression
Other outcomes:
Locations:
city: Caen
country: France
facility: Hospital of Caen
city: Chartres
country: France
facility: Hospital of Chartres
city: Clermont-Ferrand
country: France
facility: Hospital Hôtel Dieu
city: Clichy
country: France
facility: Beaujon's Hospital
city: Colmar
country: France
facility: CHR of Colmar
city: Créteil
country: France
facility: Hospital Henri Mondor
city: Paris
country: France
facility: Hospital Tarnier-Cochin
city: Paris
country: France
facility: Hospital Saint Louis, Department of P. Morel
city: Paris
country: France
facility: Hospital Saint-Louis, department of L. Dubertret
city: Paris
country: France
facility: Hospital Bichat
city: Reims
country: France
facility: Hospital of Reims
city: Rennes
country: France
facility: Hospital Pontchaillou
city: Rennes
country: France
facility: Eugène Marquis Center
city: Rouen
country: France
facility: Hospital Charles Nicolle
Study officials:
affiliation: Dermatology Department, Hospital Bichat, Paris, France
name: Eve Maubec, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maubec E, Duvillard P, Velasco V, Crickx B, Avril MF. Immunohistochemical analysis of EGFR and HER-2 in patients with metastatic squamous cell carcinoma of the skin. Anticancer Res. 2005 Mar-Apr;25(2B):1205-10.
citation: Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001 Mar 29;344(13):975-83. doi: 10.1056/NEJM200103293441306. No abstract available.
citation: Shimizu T, Izumi H, Oga A, Furumoto H, Murakami T, Ofuji R, Muto M, Sasaki K. Epidermal growth factor receptor overexpression and genetic aberrations in metastatic squamous-cell carcinoma of the skin. Dermatology. 2001;202(3):203-6. doi: 10.1159/000051637.
citation: Huang SM, Bock JM, Harari PM. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res. 1999 Apr 15;59(8):1935-40.
citation: Barbara A Burtness, Yi Li, William Flood, Bassam I Mattar, Arlene A Forastiere. Phase III trial comparing cisplatin (C) + placebo (P) to C + anti-epidermal growth factor antibody (EGF-R) C225 in patients (pts) with metastatic/recurrent head & neck cancer (HNC). Journal of Clinical Oncology,2002 ASCO Annual Meeting Proceedings. Abstract 901.
citation: Nemunaitis JJ, Eiseman I, Cunningham C et al. A phase I trial of CI-1033, a pan-erbB tyrosine kinase inhibitor, given daily for 14 days every 3 weeks, in patients with advanced solid tumors. Proc Am Soc Clin Oncol 22: page 243, 2003 (abstr 974).
citation: Maubec E, Petrow P, Scheer-Senyarich I, Duvillard P, Lacroix L, Gelly J, Certain A, Duval X, Crickx B, Buffard V, Basset-Seguin N, Saez P, Duval-Modeste AB, Adamski H, Mansard S, Grange F, Dompmartin A, Faivre S, Mentre F, Avril MF. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol. 2011 Sep 1;29(25):3419-26. doi: 10.1200/JCO.2010.34.1735. Epub 2011 Aug 1.