Malignant Pleural Mesothelioma
Conditions
Keywords
mesothelioma, chemotherapy, translational research, axitinib
Brief summary
The purpose of this study is to investigate the effects of axitinib, a potent angiogenesis inhibitor, on tissue and clinical outcome in combination with chemotherapy given to patients with mesothelioma
Detailed description
To determine the effects of the addition of axitinib to standard chemotherapy on tissue samples with respect to micro-vessel density (MVD): expression of VEGF-Receptor; PDGF receptor expression; extent of necrosis and apoptosis. To determine the safety of the addition of axitinib (to a maximum of the recommended dose of maximally 2 x 10 mg per day) to the standard treatment with cisplatin and pemetrexed. To determine the feasibility of performing a (second) thoracoscopy after 10 weeks of the combination treatment with cisplatin, pemetrexed and axitinib. Serum samples will be collected and tested for inhibiting effects in a tube formation and spheroid sprouting assay.
Interventions
BIOLOGICALaxitinib
axitinib: 5 mg BID, day 2 until day 21 of each cycle; cisplatin: 75 mg/m2 day 1, every 3 weeks; pemetrexed: 500 mg/m2 day 1, every 3 weeks.
DRUGchemotherapy
cisplatin: 75 mg/m2 day 1, every 3 weeks; pemetrexed: 500 mg/m2 day 1, every 3 weeks.
Sponsors
Pfizer
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* histologically or cytologically diagnosed malignant mesothelioma * age \> 18 years * Medically suitable for limited surgical intervention (pleural biopsies or limited pleurectomy) * Measurable or evaluable disease is not required * Ability to understand the study and give signed informed consent 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 or serum chemistries at study entry: Hematology: * ANC=\>1.5 x 109/L, * Platelets=\>150 x 109/L, * Hemoglobin =\> 6,0 mmol/l Chemistry: * total serum bilirubin \< UNL; * AST and ALT= \< 2.5xUNL, * AP \< 5xUNL (unless bone metastases are present in the absence or any liver disease) * Serum creatinine =\< 2xUNL
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 CTC,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 * Impaired renal function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To test the impact of the addition of axitinib to standaard chemotherapy treatment on histology samples | micro-vessel density;expression of VEGF and PDGF receptor; extent of necrosis and apoptosis | To determine the effects of the addition of axitinib to standard chemotherapy on tissue samples with respect to micro-vessel density (MVD); expression of VEGF-Receptor; PDGF receptor expression; extent of necrosis and apoptosis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the side effects of the standard chemotherapy and the additional risks related to axitinib use | AE;SAE;SUSAR | hypertension, fatigue, abdominal discomfort |
Countries
Netherlands
Outcome results
None listed