Cetuximab for Unresectable Cutaneous Squamous Cell Carcinoma - A National Retrospective Study

Study Overview
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Brief Summary
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Localized cutaneous squamous cell carcinoma (CSCC) is usually treated by radical surgery with or without radiotherapy. The cure rate is high around 90% of cases (1). Unresectable CSCC represents less than 10% of all CSCC. The prognosis of these advanced forms is poor, without any proven treatment option. The number of studies investigating systemic treatment of advanced or metastatic CSCC is limited, mostly based on phase II trials or case reports. Systemic treatment includes cytotoxic chemotherapy such as cisplatin and 5-Fluoro-uracil (5FU), immunotherapy (interferon alpha) or retinoic acid (13CRa) (1,2). Recently, epidermal growth factor receptor (EGFR) targeting agents have been explored (1,2). The anti-EGFR monoclonal antibody Cetuximab has shown some clinical efficacy in advanced CSCC alone or concomitant with radiotherapy or chemotherapy (3-5). A recent phase II study aimed at investigating the role of Cetuximab in 36 patients with unresectable CSCC (6). The authors reported a disease control rate at 6 weeks of 69% (95% CI, 52% to 84%). The best responses were eight partial responses and two complete responses. There were no Cetuximab-related deaths. There were three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grade 1 to 2 acne-like rash occurred in 78% of patients and was associated with prolonged Progression Free Survival (PFS) (6). The authors concluded that regarding the Cetuximab therapeutic index it could be interesting in this particular situation mainly for elderly patient. Unfortunately, the small number of patient included not allowed to draw definitive conclusion. It was interesting to note that the Disease rate control (DRC) with Cetuximab increased of 15% comparatively of DRC with chemotherapy. Additionally it seems that in case of efficacy the functional improvement of Cetuximab-sensitive patients occurred after very few infusions. Taking these data together it seemed logical to design a larger retrospective clinical trial to confirm these results in real life patients.

Official Title
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Cetuximab for Unresectable Cutaneous Squamous Cell Carcinoma - A National Retrospective Study

Conditions
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Squamous Cell Cutaneous Carcinoma of the Skin

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically Confirmed squamous cell cutaneous carcinoma of the skin (SCCS) Locally advanced SCCS that is surgically unresectable, or metastatic SCCS, with documented progression, and who received a treatment of Cetuximab in monotherapy, Patients have to be anti EGFR-naïve, Age ≥ 18 years Eastern Cooperative Oncology Group performance status ≤ 2; life expectancy ≥ 3 months Presence of at least one measurable target lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria Adequate hematologic, hepatic, and renal functions Available medical data Chemotherapy naïve patient in metastatic or locally advanced conditions (Cisplatinum used concomitantly with radiotherapy is allowed) Exclusion criteria Prior radiotherapy within the last 4 weeks before the start of cetuximab (radiotherapy in concomitance with cetuximab is allowed if this is administrated in another lesion than the lesion treated by Cetuximab). Prior therapy with an agent that targets EGFR Instable systemic diseases or active uncontrolled infections.

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit of Cetuximab at 6 weeks | To Assess the clinical benefit (complete response [CR], partial response [PR], or stable disease [SD]) after 6 weeks of treatment with Cetuximab | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate ORR | The ORR will be defined as the sum of partial responses plus complete responses after 6 weeks of treatment with Cetuximab. | December 2017 | 
| Overall survival OS | 2. The OS will be calculated between date of treatment beginning (Cetuximab) and the date of death for any reason. Patients who did not die at the time of analysis or are lost of follow-up will be censored at the date of the latest news. | December 2017 | 
| Progression free survival PFS | The PFS will be calculated between date of treatment beginning (Cetuximab) and date of progression, death or starting another anticancer treatment. Patients who did not progress, did not die at the time of analysis or are lost of follow-up will be censored at the date of the latest news. | December 2017 | 
| Cetuximab safety | The safety profile will be described using the common toxicity criteria from the NCI v4.03 and biological, including occurrence of acne-like rash. | December 2017 | 
| Overall response delay | The DOR will be measured from the time measurement criteria are first met for CR/PR until the first date that progressive disease is objectively documented (without other anticancer treatment). | December 2017 | 
| Disease stabilization delay | The DSD will be measured from the start of the treatment until the criteria for progression is objectively documented. | December 2017 | 
| Best overall response BOR | The BOR will be recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation. | December 2017 |