Standard Chemotherapy With of Without Axitinib in Malignant Mesothelioma

Malignant Pleural Mesothelioma Clinical Trial

— N08CPA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01211275
• Other study ID #: NL25655.031.08
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 27, 2010
• Last updated: February 27, 2017
• Start date: May 22, 2009
• Est. completion date: May 6, 2013

Study information

• Verified date: February 2017
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 6, 2013
• Est. primary completion date: November 13, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

Biological:
• axitinib
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.

Drug:
• chemotherapy
cisplatin: 75 mg/m2 day 1, every 3 weeks; pemetrexed: 500 mg/m2 day 1, every 3 weeks.

Locations

Country	Name	City	State
Netherlands	Antoni van Leeuwenhoekziekenhuis (NKI-AVL)	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Pfizer

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To test the impact of the addition of axitinib to standaard chemotherapy treatment on histology samples	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	micro-vessel density;expression of VEGF and PDGF receptor; extent of necrosis and apoptosis
Secondary	the side effects of the standard chemotherapy and the additional risks related to axitinib use	hypertension, fatigue, abdominal discomfort	AE;SAE;SUSAR