Nintedanib as Switch Maintenance Treatment of Pleural Malignant Mesothelioma

NCT02863055 | Terminated Phase 2 DMC

• 1 other identifier: EORTC-08112
• Study Type: interventional
• Target: 37
• Locations: 3 countries
• Sites: 9

Brief Summary

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

Conditions

Malignant Pleural Mesothelioma

Keywords

MPM; Unresectable; Phase II; Randomized; Maintenance

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  From randomization until progression or death

  6 months

Secondary Outcomes (2)

• Overall survival

  12 months

• Overall Response Rate

  6 months

Study Arms (2)

Nintedanib

EXPERIMENTAL

200 mg twice a day per os

Drug: Nintedanib

Placebo

PLACEBO COMPARATOR

Placebo match twice a day per os

Drug: Placebo

Interventions

Nintedanib DRUG

Nintedanib 200 mg administered twice daily

Nintedanib

Placebo DRUG

Matching placebo administered twice daily

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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);

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (9)

UZ Antwerpen

Antwerp, Belgium

Location

UZ Gent

Ghent, Belgium

Location

Ospedale San Paolo

Milan, Italy

Location

Manchester University NHS Foundation Trust - UHSM-Wythenshawe Hospital

Wythenshawe, Manchester, M23 9LT, United Kingdom

Location

Royal Marsden Hospital

Chelsea, United Kingdom

Location

Royal Marsden Hospital - Kingston

Kingston, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital

Sheffield, United Kingdom

Location

NHS South Tyneside-South Tyneside District Hospital

South Shields, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

nintedanib

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

Study Officials

• Sanjay Popat, PhD, MD

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Omar Abdel-Rahman, MD

  Ain Shams University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 11, 2016
• Study Start: February 4, 2018
• Primary Completion: October 12, 2023
• Study Completion: January 10, 2024
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); IT (1); GB (6)