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

NCT01098266 | Completed Phase 3 Results DMC

• 2 other identifiers: NGR0152009-016879-29
• Study Type: interventional
• Target: 400
• Locations: 12 countries
• Sites: 49

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.

Conditions

Malignant Pleural Mesothelioma

Keywords

MPM; NGR-hTNF; NGR-hTNF plus BIC; Randomized double-blind phase III study

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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

  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 (6)

• 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

• Disease Control Rate (DCR)

  Assessed every 6-12 weeks, up to 100 weeks

• Number of Partecipants With Disease Control for ≥ 6 Months

  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)

Study Arms (2)

A: NGR-hTNF + BIC

EXPERIMENTAL

NGR-hTNF plus Best Investigator's Choice

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

B: Placebo+BIC

PLACEBO COMPARATOR

Placebo plus Best Investigator's Choice

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

Interventions

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

Also known as: NGR-hTNF+BIC

A: NGR-hTNF + BIC

Placebo plus Best Investigator's Choice (BIC) 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)

Also known as: Placebo+BIC

B: Placebo+BIC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (49)

Wilshire Oncology Medical Group

Corona, California, 92879, United States

Location

City of Hope-Comprehensive Cancer Cente

Duarte, California, 91010, United States

Location

H. Lee Moffitt ancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

UTsouthwestern medical center

Dallas, Texas, 75390, United States

Location

Antwerp University Hospital

Edegem, Antwerp, B-2650, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, Liege, 4000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Cliniques Universitarie St. Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis

Ghent, 9000, Belgium

Location

UAB - Alberta Cancer Board - Cross Cancer Institute

Edmonton, Alberta, T6G1Z2, Canada

Location

University Health Network, Princess Margaret Hospital

Toronto, Ontario, M5G2C4, Canada

Location

National Cancer Institute

Cairo, 11796, Egypt

Location

Hôpitaux de Marseille Hôpital Nord

Marseille, Cedex 20, France

Location

St James's Hospital

Dublin, Ireland

Location

Ospedale Santo Spirito

Casale Monferrato, Alessandria, 15033, Italy

Location

Azienda Ospedaliera Universitaria San Luigi Gonzaga

Orbassano, Torino, 10043, Italy

Location

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

Alessandria, 15100, Italy

Location

Centro di Riferimento Oncologico

Aviano, Italy

Location

Ospedale Valduce

Como, Italy

Location

Azienda Ospedaliero-Universitaria Careggi di Firenze

Florence, Italy

Location

Istituto Nazionale per la Ricerca sul Cancro

Genoa, 16132, Italy

Location

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

Meldola, 47014, Italy

Location

Fondazione San Raffaele del Monte Tabor

Milan, 20132, Italy

Location

Azienda Ospedaliera San Gerardo

Monza, 20052, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, Italy

Location

Azienda Unità Sanitaria locale di Ravenna

Ravenna, 48100, Italy

Location

A.O. Salvini Garbagnate, Ospedale di Rho

Rho, Italy

Location

Azienda Ospedaliera Senese

Siena, 53100, Italy

Location

St. Jansdal Hospital

Harderwijk, Gelderland, 3840, Netherlands

Location

St. Antonius Hospital

Nieuwegein, Utrecht, 3435, Netherlands

Location

Medical University of Gdansk

Gdansk, 80211, Poland

Location

Maria Sklodowska Memorial Cancer Center and Institute of Oncology

Warsaw, 02-781, Poland

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

The University Hospital

Linköping, 581 85, Sweden

Location

Chest Clinic, Wythenshawe Hospital

Manchester, Greater Manchester, M23 9LT, United Kingdom

Location

Kent Oncology Centre Maidstone Hospital

Maidstone, Kent, ME16 9QQ, United Kingdom

Location

University Hospitals of Leicester

Leicester, Leicestershire, LE0116, United Kingdom

Location

Mount Vernon Cancer Centre

Middlesex, Northwood, HA6 2RN, United Kingdom

Location

Edinburgh Cancer Centre, Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12, United Kingdom

Location

The Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Location

Castle Hill Hospital

Cottingham, Yorkshire, HU16 5JQ, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29753703 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

tumor necrosis factor-alpha, CNGRC fusion protein, human

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Operations
• Organization: Molmed S.p.A

clinical.operations@molmed.com

003902212771

Study Officials

• Antonio Lambiase, MD

  AGC Biologics S.p.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2010
• First Posted: April 2, 2010
• Study Start: April 12, 2010
• Primary Completion: April 29, 2014
• Study Completion: December 1, 2017
• Last Updated: September 17, 2019
• Results First Posted: September 17, 2019

Record last verified: 2019-08

Locations

PL (2); SE (1); IT (15); ES (2); GB (10); BE (5); CA (2); FR (1); IE (1); NL (2); EG (1); US (7)