Study of NGR-hTNF as Single Agent in Patients Affected by Advanced or Metastatic Malignant Pleural Mesothelioma

Study Overview
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Brief Summary
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The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic malignant pleural mesothelioma patients treated with NGR-hTNF as single agent. Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria.

Detailed Description
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This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic malignant pleural mesothelioma previously treated with no more than one systemic therapeutic regimen , that will be conducted using Simon's two-stage design method.

Official Title
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NGR010: A Phase II Study of NGR-hTNF Administered as Single Agent Every 3 Weeks or Weekly in Patients Affected by Advanced or Metastatic Malignant Pleural Mesothelioma Previously Treated With no More Than One Systemic Therapeutic Regimen

Conditions
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Malignant Pleural Mesothelioma

Intervention / Treatment
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* Drug: NGR-hTNF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >18 years affected by malignant pleural mesothelioma previously treated with no more than one systemic therapeutic regimen Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatous, mixed Prior intrapleural cytotoxic agents including bleomycin not considered systemic chemotherapy ECOG Performance status 0 - 2 Adequate baseline bone marrow, hepatic and renal function, defined as follows: Neutrophils > 1.5 x 10^9/L and platelets > 100 x 10^9/L Bilirubin < 1.5 x ULN AST and/or ALT < 2.5 x ULN in absence of liver metastasis AST and/or ALT < 5 x ULN in presence of liver metastasis Serum creatinine < 1.5 x ULN Absence of any conditions in which hypervolemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or haemodilution could represent a risk for the patient (take as reference Technical data sheet human albumin specifically used in Pharmacy Department for NGR-hTNF dilution) Patients may have had prior therapy providing the following conditions are met: Chemotherapy and radiotherapy: wash-out period of 28 days Surgery: wash-out period of 14 days Normal cardiac function and absence of uncontrolled hypertension Patients must give written informed consent to participate in the study Exclusion Criteria: Concurrent anticancer therapy Patients may not receive any other investigational agents while on study Clinical signs of CNS involvement Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NGR-hTNF<br>NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion every 3 weeks or weekly | Drug: NGR-hTNF<br>* iv q3W or q1W 0.8 mcg/sqm NGR-hTNF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor activity defined as progression free survival (PFS) | Defined as the time from the date of randomization until disease progression, or death | during the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Growth Control Rate (TGCR) | Evaluated according to modified RECIST criteria for Malignant Pleural Mesothelioma | Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD | 
| Overall survival (OS) | Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive | from the randomization until to the date of patient death or discontinuation from the study | 
| Experimental Imaging Study (DCE-MRI) | To document possible modifications on vessels permeability by imaging techniques | During the treatment | 
| Cmax of NGR-hTNF in patients treated with weekly schedule | to evaluate Cmax of NGR-hTNF administered weekly | During the treatment | 
| AUC(tau) of NGR-hTNF in patients treated with weekly schedule | to evaluate AUC(tau) of NGR-hTNF administered weekly | During the treatment | 
| Safety according to NCI-CTCAE criteria (version 3) | To evaluate safety profile related to NGR-hTNF | During the treatment and during the follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGR-hTNF, malignant pleural mesothelioma