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

NCT ID: NCT01098266

Last Updated: 2019-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-12
• Study Completion Date: 2017-12-31

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.

Conditions

Malignant Pleural Mesothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

A: NGR-hTNF + BIC

NGR-hTNF plus Best Investigator's Choice

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

• NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
• Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
• Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles

2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles

3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

B: Placebo+BIC

Placebo plus Best Investigator's Choice

Group Type: PLACEBO_COMPARATOR

Placebo plus Best Investigator's Choice (BIC)

Intervention Type: DRUG

• Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
• Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
• Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles

2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles

3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Interventions

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

• NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
• Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
• Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles

2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles

3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Intervention Type: DRUG

Placebo plus Best Investigator's Choice (BIC)

• Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
• Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
• Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles

2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles

3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Intervention Type: DRUG

Other Intervention Names

NGR-hTNF+BIC; Placebo+BIC

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AGC Biologics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Lambiase, MD

Role: STUDY_DIRECTOR

AGC Biologics S.p.A.

Locations

Wilshire Oncology Medical Group

Corona, California, United States

City of Hope-Comprehensive Cancer Cente

Duarte, California, United States

H. Lee Moffitt ancer Center and Research Institute

Tampa, Florida, United States

Johns Hopkins

Baltimore, Maryland, United States

Columbia University

New York, New York, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

UTsouthwestern medical center

Dallas, Texas, United States

Antwerp University Hospital

Edegem, Antwerp, Belgium

Centre Hospitalier Universitaire de Liège

Liège, Liege, Belgium

Institut Jules Bordet

Brussels, , Belgium

Cliniques Universitarie St. Luc

Brussels, , Belgium

Universitair Ziekenhuis

Ghent, , Belgium

UAB - Alberta Cancer Board - Cross Cancer Institute

Edmonton, Alberta, Canada

University Health Network, Princess Margaret Hospital

Toronto, Ontario, Canada

National Cancer Institute

Cairo, , Egypt

Hôpitaux de Marseille Hôpital Nord

Marseille, , France

St James's Hospital

Dublin, , Ireland

Ospedale Santo Spirito

Casale Monferrato, Alessandria, Italy

Azienda Ospedaliera Universitaria San Luigi Gonzaga

Orbassano, Torino, Italy

Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

Alessandria, , Italy

Centro di Riferimento Oncologico

Aviano, , Italy

Ospedale Valduce

Como, , Italy

Azienda Ospedaliero-Universitaria Careggi di Firenze

Florence, , Italy

Istituto Nazionale per la Ricerca sul Cancro

Genoa, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST

Meldola, , Italy

Fondazione San Raffaele del Monte Tabor

Milan, , Italy

Azienda Ospedaliera San Gerardo

Monza, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Azienda Unità Sanitaria locale di Ravenna

Ravenna, , Italy

A.O. Salvini Garbagnate, Ospedale di Rho

Rho, , Italy

Azienda Ospedaliera Senese

Siena, , Italy

St. Jansdal Hospital

Harderwijk, Gelderland, Netherlands

St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands

Medical University of Gdansk

Gdansk, , Poland

Maria Sklodowska Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Vall d'Hebron

Barcelona, , Spain

The University Hospital

Linköping, , Sweden

Chest Clinic, Wythenshawe Hospital

Manchester, Greater Manchester, United Kingdom

Kent Oncology Centre Maidstone Hospital

Maidstone, Kent, United Kingdom

University Hospitals of Leicester

Leicester, Leicestershire, United Kingdom

Mount Vernon Cancer Centre

Middlesex, Northwood, United Kingdom

Edinburgh Cancer Centre, Western General Hospital

Edinburgh, Scotland, United Kingdom

The Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

The Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Castle Hill Hospital

Cottingham, Yorkshire, United Kingdom

Guy's Hospital

London, , United Kingdom

The Royal Marsden Hospital

London, , United Kingdom

Countries

United States; Belgium; Canada; Egypt; France; Ireland; Italy; Netherlands; Poland; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29753703 (View on PubMed)

Other Identifiers

2009-016879-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NGR015

Identifier Type: -

Identifier Source: org_study_id