NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed

AGC Biologics

Status and phase

Completed

Phase 3

Conditions

Malignant Pleural Mesothelioma

Treatments

Drug: Placebo plus Best Investigator's Choice (BIC)

Drug: NGR-hTNF plus Best Investigator's Choice (BIC)

Study type

Interventional

Funder types

Industry

Identifiers

NCT01098266

NGR015

2009-016879-29 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

400 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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