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

• ClinicalTrials.gov Identifier: NCT01211275
• Recruitment Status: Completed
• First Posted: September 29, 2010
• Last Update Posted: February 28, 2017
• Sponsor: The Netherlands Cancer Institute
• Collaborator: Pfizer
• Information provided by (Responsible Party): The Netherlands Cancer Institute

Study Description

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

Condition or disease	Intervention/treatment	Phase
Malignant Pleural Mesothelioma	Biological: axitinib; Drug: chemotherapy	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 22, 2009
• Actual Primary Completion Date: November 13, 2012
• Actual Study Completion Date: May 6, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. To test the impact of the addition of axitinib to standaard chemotherapy treatment on histology samples [ Time Frame: 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 :

1. the side effects of the standard chemotherapy and the additional risks related to axitinib use [ Time Frame: AE;SAE;SUSAR ]
   hypertension, fatigue, abdominal discomfort

Eligibility Criteria

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

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

Contacts and Locations

Locations

Netherlands

Antoni van Leeuwenhoekziekenhuis (NKI-AVL)

Amsterdam, Noord-Holland, Netherlands, 1066 CX

Sponsors and Collaborators

The Netherlands Cancer Institute

Pfizer

Investigators

• Principal Investigator: P Baas, Dr.; NKI-AvL

More Information

• Responsible Party: The Netherlands Cancer Institute
• ClinicalTrials.gov Identifier: NCT01211275
• Other Study ID Numbers: NL25655.031.08
• First Posted: September 29, 2010
• Last Update Posted: February 28, 2017
• Last Verified: February 2017

Keywords provided by The Netherlands Cancer Institute:

mesothelioma; chemotherapy; translational research; axitinib

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Cisplatin; Pemetrexed; Axitinib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors