Standard Chemotherapy With of Without Axitinib in Malignant Mesothelioma
- Conditions
- Malignant Pleural Mesothelioma
- Interventions
- Biological: axitinibDrug: chemotherapy
- Registration Number
- NCT01211275
- Lead Sponsor
- The Netherlands Cancer Institute
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description arm 2 axitinib axitinib + cisplatin + premetrexed arm 1 chemotherapy cisplatin + premetrexed
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method the side effects of the standard chemotherapy and the additional risks related to axitinib use AE;SAE;SUSAR hypertension, fatigue, abdominal discomfort
Trial Locations
- Locations (1)
Antoni van Leeuwenhoekziekenhuis (NKI-AVL)
🇳🇱Amsterdam, Noord-Holland, Netherlands