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

Skin Diseases Clinical Trial

— CTXSCC  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00240682
• Other study ID #: 2005-001098-82
• Status: Completed
• Phase: Phase 2
• First received: October 17, 2005
• Last updated: February 18, 2012
• Start date: October 2005
• Est. completion date: June 2009

Study information

• Verified date: August 2009
• Source: Centre Hospitalier of Chartres
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: June 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Skin Diseases
• Skin Neoplasms

Intervention

Drug:
• cetuximab
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.

Locations

Country	Name	City	State
France	Hospital of Caen	Caen
France	Hospital of Chartres	Chartres
France	Hospital Hôtel Dieu	Clermont-Ferrand
France	Beaujon's Hospital	Clichy
France	CHR of Colmar	Colmar
France	Hospital Henri Mondor	Créteil
France	Hospital Bichat	Paris
France	Hospital Saint Louis, Department of P. Morel	Paris
France	Hospital Saint-Louis, department of L. Dubertret	Paris
France	Hospital Tarnier-Cochin	Paris
France	Hospital of Reims	Reims
France	Eugène Marquis Center	Rennes
France	Hospital Pontchaillou	Rennes
France	Hospital Charles Nicolle	Rouen

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier of Chartres	Hospital of Chartres- France

Country where clinical trial is conducted

France, 

References & Publications (7)

Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001 Mar 29;344(13):975-83. Review. — View 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.

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. — View 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. — View 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, Mentré F, Avril MF. Phase II study of cetu — View 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).

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease control rate assessed by CT or MRI		6 weeks	No
Secondary	Safety profile.		during treatment or within 30 days after the final administration with a cut-off date at week 48.	Yes
Secondary	Time to disease progression.		number of days from the start of treatment to the earliest day of progressive disease	No
Secondary	Overall survival.		from the first infusion until week 48 or death	No
Secondary	Duration of response in responder patients at 6 weeks.		time to disease progression	No