A Study of Cetuximab Combined With Cisplatin or Carboplatin/Pemetrexed as First Line Treatment in Patients With Malignant Pleural Mesothelioma.

Study Overview
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Brief Summary
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Multicenter, open phase 2 study on patients with malignant mesothelioma. Standardly, 4 to 6 cycles of palliative chemotherapy, platinum in combination with pemetrexed, are given. Despite of this treatment, median survival is poor (9-12 months). By combining conventional cytotoxic agents with a novel agent, hopefully treatment and survival can be approved. Cetuximab or Erbitux is a monoclonal antibody against the EGFR (Epidermal Growth Factor Receptor). By blocking the receptor, it interferes with cel growth and division. Most mesothelioma show a strong expression of the EGFR protein. Apart from that, Cetuximab also has antibody-dependent cell-mediated cytotoxicity (ADCC). In this trial, patients will be treated with standard chemotherapy, combined with Cetuximab weekly. After a maximum of 6 cycles of chemotherapy, administration of Cetuximab will be continued until disease progression. Every 6 weeks, a CT scan will be done to evaluate therapy. Most common side effect of Cetuximab is acneiform rash. The translation research program consists of the determination of EGFR- and K-Ras mutations on the tumor tissue and the correlation with outcome. In the first part of the trial, 18 patients will be included. After a positive interim analysis, a total of 43 patients will be included.

Official Title
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Phase II Study of Cetuximab Combined With Cisplatin or Carboplatin/Pemetrexed as First Line Treatment in Patients With Malignant Pleural Mesothelioma.

Conditions
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Cancer

Intervention / Treatment
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* Drug: Cetuximab (Erbitux)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven malignant pleural mesothelioma, epitheloid subtype Recurrent after radical surgery or disease not considered suitable for radical treatment EGFR IHC + as assessed by DAKO kit with at least 1% of cells showing staining Performance status WHO 0 or 1 Life expectancy > 12 weeks Weight loss < 10% in last 3 months Adequate bone marrow reserve, renal and hepatic function Measurable disease (modified RECIST) No prior chemotherapy No prior or other malignancies, except if longer than 5 yrs ago and adequately treated or basocellular skin or in situ cervical cancer No uncontrolled infection Written informed consent. Male/Female > 18 years Exclusion Criteria: Evidence of brain or leptomeningeal metastases Patients who are unable to interrupt aspirin, other nonsteroidal anti-inflammatory drugs for a 5-day period starting 2 days before administration of pemetrexed (8-day period for long acting agents such as piroxicam) Patients that cannot be treated with folic acid and vitamin B 12 Patients that cannot be treated with dexamethasone. Presence of clinically detectable (by physical examination) third-space fluid collections, for example ascites of pleural effusions that cannot be controlled by drainage or other procedures prior to the study entry. Use of investigational drugs

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 (Erbitux)<br> | Drug: Cetuximab (Erbitux)<br>* Patients will be treated with standard chemotherapy (4-6 cycles), combined with weekly administration of Cetuximab (Erbitux) until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression fee survival rate |  | At 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate according to modified RECIST criteria |  | every 6 weeks until progression | 
| Toxicity (CTCAE version 4) |  | weekly during treatment and follow-up of AE's until 30 days after last dosis | 
| Overall survival |  | average survival of 9 - 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant mesothelioma