Nintedanib as Switch Maintenance Treatment of Pleural Malignant Mesothelioma (NEMO)

Nintedanib as Maintenance Treatment of Pleural Malignant Mesothelioma (NEMO): a Randomized Double Blinded Phase II Study of the EORTC Lung Cancer Group

This is a multicenter, randomized, 1:1, double blinded phase II trial. Patients with unresectable malignant pleural mesothelioma (MPM) will be randomized between arm A: nintedanib and arm B:placebo

Study Overview

• Status: Terminated
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Drug: Nintedanib; Drug: Placebo

Detailed Description

This is a multicenter, prospective, double blinded, randomized, two-arm phase II trial aiming to evaluate nintedanib treatment as switch maintenance in patients with unresectable MPM.

After signing of the informed consent and upon confirmation of all eligibility criteria, patients will be randomized 1:1 to:

• Arm A: twice daily nintedanib at a dose of 200 mg until progression or unacceptable toxicities.
• Arm B: matched placebo.

Response evaluation will be performed through CT scans every 8 weeks.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • UZ Antwerpen
  • Ghent, Belgium
    • UZ Gent
• Italy
  • Milan, Italy
    • Ospedale San Paolo
• United Kingdom
  • Chelsea, United Kingdom
    • Royal Marsden Hospital
  • Kingston, United Kingdom
    • Royal Marsden Hospital - Kingston
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospitals Nhs Foundation Trust - Weston Park Hospital
  • South Shields, United Kingdom
    • NHS South Tyneside-South Tyneside District Hospital
  • Sutton, United Kingdom
    • Royal Marsden Hospital
  • Manchester
    • Wythenshawe, Manchester, United Kingdom, M23 9LT
      • Manchester University NHS Foundation Trust - UHSM-Wythenshawe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological diagnosis of unresectable Malignant Pleural Mesothelioma (MPM);
• Response or Stable disease according to modified RECIST criteria [48] after first line platinum-pemetrexed chemotherapy for 4-6 cycles;
• Last platinum chemotherapy dose administered within 60 days (i.e. randomization must occur within 60 days from the last dose of the last cycle of platinum-pemetrexed chemotherapy);
• Age >18 years;
• ECOG performance status (PS) 0-2;
• Life expectancy of at least 12 weeks in the opinion of the investigator;
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose

Exclusion Criteria:

• prior systemic anticancer therapy including cytotoxic therapy or immune-checkpoint inhibitor, for MPM, other than first line platinum-based doublet chemotherapy;
• previous extra-pleural pneumonectomy (other forms of previous surgery eg pleurectomy are acceptable);
• previous Vascular Endothelial Growth Factor (VEGF) inhibitors (eg bevacizumab, sorafenib, etc);
• treatment with other investigational drugs or treatment in another clinical interventional trial within the past 4 weeks before start of therapy or concomitantly with the trial;
• patients that, in the opinion of the investigator, have reduced performance status by 2 ECOG levels (e.g. PS 0 to 2 or PS 1 to 3) from beginning to completion of 1st line chemotherapy;
• radiotherapy (with the exception of palliative radiotherapy) during study or within 4 weeks of start of study drug;
• known brain metastasis or lepto-meningeal disease. Patients with suspicious neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasisNo active brain metastases (e.g. stable for < 4 weeks;, no adequate previous treatment with radiotherapy;, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization); patients with suspicious neurological symptoms should undergo a CT scan/MRI of the brain to assess brain metastasis;
• leptomeningeal metastases;
• significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial;
• pre-existing clinically significant ascites and/or clinically significant pleural effusion;
• active or history of bleeding complications that would prevent anti-angiogenic therapy
• centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels; typical mediastinal pleural involvement with mesothelioma remains eligible;
• clinically active cancer other than mesothelioma within 5 years prior to start of study treatment;
• radiographic evidence of cavitatory or necrotic tumors;
• unstoppable use of therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =325mg per day);
• clinically significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months, congestive New York Heart Association (NYHA) II, serious cardiac arrhythmia, clinically significant pericardial effusion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nintedanib; 200 mg twice a day per os	Drug: Nintedanib; Nintedanib 200 mg administered twice daily
Placebo Comparator: Placebo; Placebo match twice a day per os	Drug: Placebo; Matching placebo administered twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	From randomization until progression or death	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From randomization until progression or death	12 months
Overall Response Rate	Response according to modified RECIST	6 months

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Principal Investigator: Sanjay Popat, PhD, MD, Royal Marsden NHS Foundation Trust; Principal Investigator: Omar Abdel-Rahman, MD, Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2018
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): January 10, 2024

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimated): August 11, 2016

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Randomized; Unresectable; Phase II; Maintenance; MPM
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Substandard Drugs; Pharmaceutical Preparations; nintedanib
• Other Study ID Numbers: EORTC-08112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No