NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed
- Conditions
- Malignant Pleural Mesothelioma
- Interventions
- Drug: Placebo plus Best Investigator's Choice (BIC)
- Registration Number
- NCT01098266
- Lead Sponsor
- AGC Biologics S.p.A.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 400
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A: NGR-hTNF + BIC NGR-hTNF plus Best Investigator's Choice (BIC) NGR-hTNF plus Best Investigator's Choice B: Placebo+BIC Placebo plus Best Investigator's Choice (BIC) Placebo plus Best Investigator's Choice
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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 Outcome Measures
Name Time Method Disease Control Rate (DCR) Assessed every 6-12 weeks, up to 100 weeks Disease control rate (DCR), defined as the percentage of patients who have a best-response rating of complete or partial response or stable disease, according to MPM-modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Number of Partecipants With Adverse Events Assessed every 6-12 weeks, up to 100 weeks All adverse events will be recorded according to CTC version 4.02 (CTC reference: http://ctep.cancer.gov/reporting/ctc.html) on the case report forms (CRFs); the investigator will decide if those events are drug related and his decision will be recorded on the forms for all adverse events.
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) Quality of life (QoL) assessment was performed by using a questionnaire according to The Lung Cancer Symptom Scale (LCSS) . The LCSS is designed as a disease and site-specific measure of QoL particularly for use in clinical trials. It evaluates six major symptoms (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain) associated with lung malignancies and their effect on overall symptomatic distress, functional activities, and global QoL. Within this trial the questionnaire according to LCSS was only recorded by the patient (patient's scale). QoL assessment was performed by using a questionnaire according to LCSS, which consists of nine 100-mm visual analog scales, with scores reported from 0 to 100 (0 representing the best score). The LCSS subscore is the average symptom burden index computed as the mean score for all six major symptoms. Symptomatic progression was defined as a worsening in the average symptom burden index by 25%.
Evaluation of Medical Care Utilization in the Two Treatment Arms Assessed every 6-12 weeks, up to 100 weeks Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters.
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 Defined as the time from the date of randomization until disease progression, or deathdue to any couse or the last patient was konwn to be alive. Progression is defined usind Response Evaluation Criteria In Solid Tumors Criteria (Recist v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition torelative increase of 20% the sum must also demonstrate an absolute increase of at least 5 mm. In addition the appearance of one or more new lesions was also considered progression
Number of Partecipants With Disease Control for ≥ 6 Months Assessed every 6-12 weeks, up to 100 weeks Measured from the date of randomization until disease progression, or death due to any cause
Trial Locations
- Locations (48)
Wilshire Oncology Medical Group
🇺🇸Corona, California, United States
Columbia University
🇺🇸New York, New York, United States
Antwerp University Hospital
🇧🇪Edegem, Antwerp, Belgium
Chest Clinic, Wythenshawe Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
UTsouthwestern medical center
🇺🇸Dallas, Texas, United States
Azienda Unità Sanitaria locale di Ravenna
🇮🇹Ravenna, Italy
Kent Oncology Centre Maidstone Hospital
🇬🇧Maidstone, Kent, United Kingdom
Ospedale Santo Spirito
🇮🇹Casale Monferrato, Alessandria, Italy
City of Hope-Comprehensive Cancer Cente
🇺🇸Duarte, California, United States
Johns Hopkins
🇺🇸Baltimore, Maryland, United States
National Cancer Institute
🇪🇬Cairo, Egypt
Maria Sklodowska Memorial Cancer Center and Institute of Oncology
🇵🇱Warsaw, Poland
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
The University Hospital
🇸🇪Linkoping, Sweden
Mount Vernon Cancer Centre
🇬🇧Middlesex, Northwood, United Kingdom
The Royal Marsden Hospital
🇬🇧London, United Kingdom
Hôpitaux de Marseille Hôpital Nord
🇫🇷Marseille, France
Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genoa, Italy
Universitair Ziekenhuis
🇧🇪Gent, Belgium
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
H. Lee Moffitt ancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Centre Hospitalier Universitaire de Liège
🇧🇪Liège, Liege, Belgium
Cliniques Universitarie St. Luc
🇧🇪Bruxelles, Belgium
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
🇮🇹Meldola, Italy
Medical University of Gdansk
🇵🇱Gdansk, Poland
UAB - Alberta Cancer Board - Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Azienda Ospedaliera Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Torino, Italy
Centro di Riferimento Oncologico
🇮🇹Aviano, Italy
University Health Network, Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
St James's Hospital
🇮🇪Dublin, Ireland
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
🇮🇹Alessandria, Italy
A.O. Salvini Garbagnate, Ospedale di Rho
🇮🇹Rho, Italy
University Hospitals of Leicester
🇬🇧Leicester, Leicestershire, United Kingdom
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
Ospedale Valduce
🇮🇹Como, Italy
Azienda Ospedaliero-Universitaria Careggi di Firenze
🇮🇹Firenze, Italy
Fondazione San Raffaele del Monte Tabor
🇮🇹Milan, Italy
Azienda Ospedaliera Senese
🇮🇹Siena, Italy
Azienda Ospedaliera San Gerardo
🇮🇹Monza, Italy
Istituto Oncologico Veneto
🇮🇹Padova, Italy
St. Jansdal Hospital
🇳🇱Harderwijk, Gelderland, Netherlands
St. Antonius Hospital
🇳🇱Nieuwegein, Utrecht, Netherlands
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Edinburgh Cancer Centre, Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom
Castle Hill Hospital
🇬🇧Cottingham, Yorkshire, United Kingdom