Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM

Study Overview
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Brief Summary
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The main objective of the trial is to document the efficacy of NGR-hTNF administered as maintenance treatment at 0.8 µg/m2 weekly in advanced malignant pleural mesothelioma

Detailed Description
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First-line treatment of advanced malignant pleural mesothelioma (MPM) is based on six cycles of a pemetrexed-based chemotherapy, with a median progression-free survival (PFS) of approximately 6 months.However, the median time from completion of first-line treatment to initiation of second-line therapy is approximately 3 months. Recent experiences in non-small cell lung cancer patients have shown that a maintenance treatment given immediately after first-line treatment regimens can improve PFS and survival. Considering the toxicity profile of NGR-hTNF characterized by mild-to-moderate constitutional symptoms registered in a phase II trial in previously treated MPM patients, as well as the disease control observed in about half of the patients and maintained for more than four months and more than nine months in the triweekly and weekly cohorts, respectively, seems justified to compare in a randomized phase II trial the time-related efficacy of NGR-hTNF against placebo in advanced MPM patients who did not progress after six cycles of a standard pemetrexed-based treatment.

Official Title
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NGR019: Randomized Double-blind Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced Malignant Pleural Mesothelioma (MPM)

Conditions
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Advanced Malignant Pleural Mesothelioma

Intervention / Treatment
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* Drug: NGR-hTNF
* Drug: Placebo
* Other: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatoid, mixed, or unknown Patients with non-progressive disease after six cycles of first-line, pemetrexed-based regimen administered for advanced or metastatic disease ECOG Performance Status 0 - 1 Life expectancy of ≥ 12 weeks Adequate baseline bone marrow, hepatic and renal function, defined as follows: Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x109/L; hemoglobin ≥ 9 g/dL Bilirubin ≤ 1.5 x ULN AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis Serum creatinine < 1.5 x ULN Measurable or non-measurable disease according to malignant pleural mesothelioma-modified RECIST criteria Patients may have had prior therapy providing the following conditions are met: Surgery: wash-out period of 14 days Radiation therapy: wash-out period of 28 days Chemotherapy: wash-out period of 21 days Patients must give written informed consent to participate in the study Exclusion Criteria: Patients must not receive any other investigational agents while on study Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication Uncontrolled hypertension QTc interval (congenital or acquired) > 450 ms History or evidence upon physical examination of Central Nervous System disease unless adequately treated 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.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: NGR-hTNF + Best Supportive Care<br>NGR-hTNF + Best Supportive Care | Drug: NGR-hTNF<br>* NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs<br>Other: Best Supportive Care<br>* Where applicable and as appropriate according to Institutional clinical practice and literature guidelines. Best supportive care includes antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis<br>|
| Placebo Comparator: Arm B: Placebo + Best Supportive Care<br>Placebo + Best Supportive Care | Drug: Placebo<br>* Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs<br>Other: Best Supportive Care<br>* Where applicable and as appropriate according to Institutional clinical practice and literature guidelines. Best supportive care includes antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Defined as the time from the date of randomization until disease progression, or death | every 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | every 6-12 weeks | 
| Tumor response | Assessed according to modified RECIST criteria for MPM | every 6 weeks | 
| Safety and Toxicity according to NCI-CTCAE criteria(version 4.03) | To evaluate safety and toxicity profile related to NGR-hTNF | during the study | 
| Quality of life assessment by using a questionnaire according to Lung Cancer Symptom Scale (LCSS) | To assess changes in quality of life (QoL) in the two treatment arms. | From date of randomization until the end of treatment, assessed every 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant Pleural Mesothelioma, MPM, Maintenance treatment, NGR-hTNF