Clinical trial NCT00996567: A Study of Cetuximab Combined With Cisplatin or Carboplatin/Pemetrexed as First Line Treatment in Patients With Malignant Pleural Mesothelioma.
Official title: Phase II Study of Cetuximab Combined With Cisplatin or Carboplatin/Pemetrexed as First Line Treatment in Patients With Malignant Pleural Mesothelioma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: Malignant mesothelioma
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2009-10-16
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression fee survival rate
timeFrame: At 18 weeks
Secondary outcomes:
measure: Response rate according to modified RECIST criteria
timeFrame: every 6 weeks until progression
measure: Toxicity (CTCAE version 4)
timeFrame: weekly during treatment and follow-up of AE's until 30 days after last dosis
measure: Overall survival
timeFrame: average survival of 9 - 12 months
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Mechelen
country: Belgium
facility: AZ St. Maarten
city: Heerlen
country: Netherlands
facility: AMC Heerlen
Study officials:
affiliation: University Hospital, Ghent
name: Veerle Surmont, MD
role: PRINCIPAL_INVESTIGATOR
References: