ngr015: study in second line for patient with advanced malignant pleural mesothelioma pretreated with pemetrexed

Conditions: Malignant Pleural Mesothelioma

Summary: the main objective of the trial is to document the efficacy of ngr-htnf administered at low dose weekly in advanced malignant pleural mesothelioma patients previously treated with a pemetrexed-based chemotherapy regimen.

currently, there are no regulatory-approved or widely accepted treatment options for patients failing a standard pemetrexed-based chemotherapy regimen. for this reason, the best supportive care (bsc) alone might be considered as a standard reference for a randomized phase iii trial in this setting. however, single-agent chemotherapeutic agents (such as doxorubicin,gemcitabine, or vinorelbine) with a well-documented safety profile and antitumor activity are also used in clinical practice. therefore, the best investigator's choice (bic) between either best supportive care alone or combined with a few selected single-agent chemotherapy (including doxorubicin, gemcitabine, or vinorelbine) might be considered as an acceptable reference arm as well in this setting. the current phase iii study aims to show a superior efficacy in terms of overall survival duration of ngr-htnf 0.8 µg/mq weekly plus bic versus placebo plus bic in advanced mpm patients progressing after a standard pemetrexed-based chemotherapy.

Eligibility criteria:
inclusion criteria: * age ≥ 18 years * histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatoid, mixed, or unknown * prior treatment with no more than one systemic pemetrexed-based chemotherapy regimen administered for advanced or metastatic disease. prior use of a biological agent in combination with a pemetrexed-based regimen and prior administration of intrapleural cytotoxic agents are allowed. patients who have previously received anthracyclines should not receive doxorubicin * ecog performance status 0 - 2 * life expectancy of ≥ 12 weeks * adequate baseline bone marrow, hepatic and renal function, defined as follows: 1. neutrophils ≥ 1.5 x 109/l; platelets ≥ 100 x 109/l; hemoglobin ≥ 9 g/dl 2. bilirubin ≤ 1.5 x uln 3. ast and/or alt ≤ 2.5 x uln in absence of liver metastasis or ≤ 5 x uln in presence of liver metastasis 4. serum creatinine \< 1.5 x uln * measurable or non-measurable disease according to mpm-modified recist criteria * patients may have had prior therapy providing the following conditions are met: 1. surgery: wash-out period of 14 days 2. systemic and radiation anti-tumor therapy: wash-out period of 28 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 cns disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke) * 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

Keywords: mpm ngr-htnf ngr-htnf plus bic randomized double-blind phase iii study