Clinical trial NCT01211275: Standard Chemotherapy With of Without Axitinib in Malignant Mesothelioma
Official title: A Randomized Phase I/II Study of Standard Chemotherapy (Cisplatin and Pemetrexed) With or Without Axitinib in Patients With Malignant Mesothelioma: Interim Biopsy Analysis to Determine Efficacy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malignant Pleural Mesothelioma
Keywords: mesothelioma
chemotherapy
translational research
axitinib
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2010-09-29
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To test the impact of the addition of axitinib to standaard chemotherapy treatment on histology samples
timeFrame: micro-vessel density;expression of VEGF and PDGF receptor; extent of necrosis and apoptosis
Secondary outcomes:
measure: the side effects of the standard chemotherapy and the additional risks related to axitinib use
timeFrame: AE;SAE;SUSAR
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekziekenhuis (NKI-AVL)
state: Noord-Holland
Study officials:
affiliation: NKI-AvL
name: P Baas, Dr.
role: PRINCIPAL_INVESTIGATOR
References: