Clinical trial NCT01098266: NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malignant Pleural Mesothelioma
Keywords: MPM
NGR-hTNF
NGR-hTNF plus BIC
Randomized double-blind phase III study
Lead sponsor: AGC Biologics S.p.A.
Sponsor class: INDUSTRY
First posted: 2010-04-02
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 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
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: Assessed every 6-12 weeks, up to 100 weeks
measure: Number of Partecipants With Disease Control for ≥ 6 Months
timeFrame: Assessed every 6-12 weeks, up to 100 weeks
measure: Number of Partecipants With Adverse Events
timeFrame: Assessed every 6-12 weeks, up to 100 weeks
measure: Time to LCSS Symptomatic Progression
timeFrame: 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)
measure: Evaluation of Medical Care Utilization in the Two Treatment Arms
timeFrame: Assessed every 6-12 weeks, up to 100 weeks
Other outcomes:
Locations:
city: Corona
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Duarte
country: United States
facility: City of Hope-Comprehensive Cancer Cente
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt ancer Center and Research Institute
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: New York
country: United States
facility: Columbia University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: UTsouthwestern medical center
state: Texas
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerp
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
state: Liege
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: Cliniques Universitarie St. Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis
city: Edmonton
country: Canada
facility: UAB - Alberta Cancer Board - Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
state: Ontario
city: Cairo
country: Egypt
facility: National Cancer Institute
city: Marseille
country: France
facility: Hôpitaux de Marseille Hôpital Nord
city: Dublin
country: Ireland
facility: St James's Hospital
city: Casale Monferrato
country: Italy
facility: Ospedale Santo Spirito
state: Alessandria
city: Orbassano
country: Italy
facility: Azienda Ospedaliera Universitaria San Luigi Gonzaga
state: Torino
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
city: Como
country: Italy
facility: Ospedale Valduce
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi di Firenze
city: Genoa
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
city: Milan
country: Italy
facility: Fondazione San Raffaele del Monte Tabor
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Ravenna
country: Italy
facility: Azienda Unità Sanitaria locale di Ravenna
city: Rho
country: Italy
facility: A.O. Salvini Garbagnate, Ospedale di Rho
city: Siena
country: Italy
facility: Azienda Ospedaliera Senese
city: Harderwijk
country: Netherlands
facility: St. Jansdal Hospital
state: Gelderland
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Utrecht
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Warsaw
country: Poland
facility: Maria Sklodowska Memorial Cancer Center and Institute of Oncology
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Linkoping
country: Sweden
facility: The University Hospital
city: Manchester
country: United Kingdom
facility: Chest Clinic, Wythenshawe Hospital
state: Greater Manchester
city: Maidstone
country: United Kingdom
facility: Kent Oncology Centre Maidstone Hospital
state: Kent
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester
state: Leicestershire
city: Middlesex
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: Northwood
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre, Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
state: Scotland
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
state: Surrey
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: Yorkshire
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: AGC Biologics S.p.A.
name: Antonio Lambiase, MD
role: STUDY_DIRECTOR
References:
citation: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. doi: 10.1016/S1470-2045(18)30193-1. Epub 2018 May 9.