Cancer
Conditions
Keywords
Malignant mesothelioma
Brief summary
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.
Interventions
Patients will be treated with standard chemotherapy (4-6 cycles), combined with weekly administration of Cetuximab (Erbitux) until disease progression.
Sponsors
Merck Sharp & Dohme LLC
University Hospital, Ghent
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression fee survival rate | At 18 weeks |
Secondary
| Measure | 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 |
Countries
Belgium, Netherlands
Outcome results
None listed