NGR015: Randomized Double-blind Phase III Study of NGR-hTNF Plus Best Investigator's Choice (BIC) Versus Placebo Plus BIC in Previously Treated Patients With Advanced Malignant Pleural Mesothelioma (MPM)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 400
- Locations
- 48
- Primary Endpoint
- Overall Survival (OS)
Study Overview
Brief 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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/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 MPM-modified RECIST criteria
- •Patients may have had prior therapy providing the following conditions are met:
- •Surgery: wash-out period of 14 days
- •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
Arms & Interventions
A: NGR-hTNF + BIC
NGR-hTNF plus Best Investigator's Choice
Intervention: NGR-hTNF plus Best Investigator's Choice (BIC) (Drug)
B: Placebo+BIC
Placebo plus Best Investigator's Choice
Intervention: Placebo plus Best Investigator's Choice (BIC) (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, wichever came first, assesed up to 48 months
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
Secondary Outcomes
- Disease Control Rate (DCR)(Assessed every 6-12 weeks, up to 100 weeks)
- Number of Partecipants With Adverse Events(Assessed every 6-12 weeks, up to 100 weeks)
- Time to LCSS Symptomatic Progression(from the date of randomization to the date of the LCSS assessment on which symptomatic progression was identified, assessed on cycle 2, cycle 4 and cycle 6 (each cycle lasted 21 days))
- Evaluation of Medical Care Utilization in the Two Treatment Arms(Assessed every 6-12 weeks, up to 100 weeks)
- Progression-Free Survival (PFS)(From the date of randomization until the date of first documented progression or date of death from any cause, wichever came first, assessed up to 48 months)
- Number of Partecipants With Disease Control for ≥ 6 Months(Assessed every 6-12 weeks, up to 100 weeks)