Study of Cetuximab in Squamous Cell Carcinoma of the Skin Expressing EGFR

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Skin Diseases, Carcinoma, Squamous Cell

Intervention / Treatment
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* Drug: cetuximab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cetuximab<br>cetuximab | Drug: cetuximab<br>* Dosage form: bottles of 50 ml, 2 mg/ml; Dosage:400 mg/m2 initial dose followed by 250 mg/m2 by infusion every week; Number of Cycles : until progression or unacceptable toxicity develops.<br>* Other names: Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate assessed by CT or MRI |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile. |  | during treatment or within 30 days after the final administration with a cut-off date at week 48. | 
| Time to disease progression. |  | number of days from the start of treatment to the earliest day of progressive disease | 
| Overall survival. |  | from the first infusion until week 48 or death | 
| Duration of response in responder patients at 6 weeks. |  | time to disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin, Carcinoma, Squamous Cell, cetuximab, epidermal growth factor receptor