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A randomized phase I/II study of standard chemotherapy (cisplatin and pemetrexed) with or without Axitinib in patients with malignant mesothelioma: interim biopsy analysis and Dynamic Contrast Enhanced MRI to determine efficacy.

Phase 2
Recruiting
Conditions
malignant mesothelioma
pleural tumor
10027412
Registration Number
NL-OMON33544
Lead Sponsor
Antoni van Leeuwenhoek Ziekenhuis
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
Not specified
Target Recruitment
26
Inclusion Criteria

•Patients with histologically or cytologically diagnosed malignant mesothelioma and age >18 years.
•Medically suitable for limited surgical intervention (pleural biopsies or limited pleurectomy).
•Not considered candidates for trimodality treatment (as part of a study).
•Measurable or evaluable disease is not required (see tumor response assessment).
•Ability to understand the study and give signed informed consent prior to beginning of protocol specific procedures including the approval to accept a second thoracoscopic or surgical treatment after the third course.
•No previous chemotherapy.
•Radiotherapy is allowed when this is given for palliation, the interval is > 4 weeks, not more than 1/3 of the bone marrow capacity or all tumor is within the irradiation field.
•WHO performance status =<2
•Adequate organ function as evidenced by the following peripheral blood counts of serum chemistries at study entry:
•Hematology: Neutrophil count => 1.5 x 109/l, Platelets => 150 x 109/l, Hemoglobin => 6,0 mmol/l.
•Chemistry: Total serum bilirubin within the upper normal limits; ASAT (SGOT) and ALAT (SGPT) =< 2.5 times the upper normal limits, AP (alkaline phosphatases) < 5x UNL (unless bone metastases are present in the absence or any liver disease).

Exclusion Criteria

•Active uncontrolled infection, severe cardiac dysfunction or uncorrectable bleeding tendency.
•Previous successful pleurodesis.
•Uncontrolled hypertension.
•Symptomatic peripheral neuropathy > grade 2 according to NCIC Common Toxicity Criteria, version 3.0.
•Presence of symptomatic CNS metastases.
•Unstable peptic ulcer, unstable diabetes mellitus or other serious disabling condition.
•Concomitant administration to any other experimental drugs under investigation.
•Creatinine clearence < 60 ml/min

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Primary Objective:<br /><br>(1) To determine the effects of the addition of axitinib to standard<br /><br>chemotherapy on tissue samples with respect to micro-vessel density (MVD);<br /><br>expression of VEGF-Receptor; PDGF receptor expression; extent of necrosis and<br /><br>apoptosis.<br /><br>(2) To determine the safety of the addition of axitinib (to a maximum of the<br /><br>recommended dose of maximally 2 x 5 mg per day) to the standard treatment with<br /><br>cisplatin and pemetrexed.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>Secondary Objective(s):<br /><br>(3) To determine the feasibility of performing a (second) thoracoscopy after 10<br /><br>weeks of the combination treatment with cisplatin, pemetrexed and axitinib.<br /><br>(4) Serum samples will be collected and tested for inhibiting effects in a tube<br /><br>formation and spheroid sprouting assay.</p><br>
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