Standard Chemotherapy With of Without Axitinib in Malignant Mesothelioma (N08CPA)

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

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

Study Overview

• Status: Completed
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Biological: axitinib; Drug: chemotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066 CX
      • Antoni van Leeuwenhoekziekenhuis (NKI-AVL)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: arm 2; axitinib + cisplatin + premetrexed	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.; Other Names: cisplatin; alimta
Active Comparator: arm 1; cisplatin + premetrexed	Drug: chemotherapy; cisplatin: 75 mg/m2 day 1, every 3 weeks; pemetrexed: 500 mg/m2 day 1, every 3 weeks.; Other Names: cisplatin; alimta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
the side effects of the standard chemotherapy and the additional risks related to axitinib use	hypertension, fatigue, abdominal discomfort	AE;SAE;SUSAR

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Pfizer
• Investigators: Principal Investigator: P Baas, Dr., NKI-AVL

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2009
• Primary Completion (Actual): November 13, 2012
• Study Completion (Actual): May 6, 2013

Study Registration Dates

• First Submitted: September 27, 2010
• First Submitted That Met QC Criteria: September 28, 2010
• First Posted (Estimate): September 29, 2010

Study Record Updates

• Last Update Posted (Actual): February 28, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: chemotherapy; mesothelioma; axitinib; translational research
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Cisplatin; Axitinib; Pemetrexed
• Other Study ID Numbers: NL25655.031.08