dENdritic Cell Therapy Combined With SURgEry in Mesothelioma

NCT05304208 | Recruiting Phase 1 DMC

• 1 other identifier: 76712
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The ENSURE trial is an open label, single center, phase 1, feasibility study. Sixteen adult patients diagnosed with resectable epithelioid malignant pleural mesothelioma (MPM) will be enrolled following first-line chemotherapy. Before standard-of-care chemotherapy, a leukapheresis will be performed and monocytes will be used for differentiation to dendritic cells (DCs) using specific cytokines. Allogeneic tumor lysate (Pheralys) loaded autologous DCs (MesoPher) will be re-injected 3 weeks after completing chemotherapy, 2 times every other week. Four weeks after the first injection with dendritic cell therapy (DCT), patients will undergo extrapleural pleurectomy/decortication (eP/D) surgery and receive three bi-weekly injections with DCT (starting 4 weeks after surgery). In total, five DC vaccinations will be administered. A tumor biopsy will be collected before starting neo-adjuvant DCT.

Conditions

Mesotheliomas Pleural

Keywords

dendritic cell therapy; malignant pleural mesothelioma; mesopher; pleurectomy/decortication

Outcome Measures

Primary Outcomes (1)

• Number of participant who are alive and have completed (neo)adjuvant DCT (5 administrations) and surgery at week 15 (+4 weeks) without extended treatment-related delay, persisting grade 3-4 treatment side-effects or evidence of progression [Feasibility]

  To determine the feasibility of DCT with Mesopher performed before and after eP/D in patients with resectable epithelioid MPM who received first line chemotherapy. Feasibility is measured by the number of patient who are alive and have completed neo-adjuvant plus adjuvant DCT (5 administrations in total or less in case of production shortage) and surgery at week 15 (+4 weeks) without extended treatment-related delay, persisting grade 3- 4 treatment side-effects or evidence of progression/relapse. Patients who markedly progressed after chemotherapy will be discontinued from the trial and will be considered as failures for assessment of the primary end-point.

  2 years

Secondary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Safety and Tolerability]

  2 years

• Median progression free and median overall survival since start of treatment [Efficacy]

  2 years

Other Outcomes (1)

• Number of participants with increased immune cell infiltration in tumor tissue induced by (neo)adjuvant DCT [Anti-tumor immune response]

  2 years

Study Arms (1)

Treatment arm

EXPERIMENTAL

Before standard-of-care chemotherapy, a leukapheresis will be performed and monocytes will be used for differentiation to DCs using specific cytokines. Allogeneic tumor lysate (Pheralys) loaded autologous DCs (MesoPher) will be re-injected 3 weeks after completing chemotherapy, 2 times every other week. Four weeks after the first injection with DCT, patients will undergo eP/D surgery and receive three bi-weekly injections with DCT (starting 4 weeks after surgery). If there is a surplus of vaccinations, a 6th and 7th vaccination at 3 and six months after the last vaccination could be considered by the treating physician.

Biological: Mesopher

Interventions

Mesopher BIOLOGICAL

autologous monocyte-derived DCs loaded with PheraLys (tumor cell lysate)

Treatment arm

Eligibility Criteria

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

You may not qualify if:

• Patients must be at least 18 years old and must be able to give written informed con-sent.
• Resectable disease defined by stage cT1-3, N0-1, M0 (I to IIIA) according to UICC TNM classification (8th edition). A fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computerized tomography (CT) scan with fusion images showing absence of M1, N2 involvement is required. Focal chest wall lesions are acceptable.
• Tumor tissue available after completing chemotherapy and before starting treatment with DCT. Tumor tissue can be obtained by either a CT-guided needle biopsy or a Video-assisted thoracoscopic surgery (VATS) biopsy.
• Fit to receive platinum-based chemotherapy (as per standard of care of the treating physician/Institution) and undergo a P/D with optional removal of hemidiaphragm and pericardium. The responsible surgeon and chest physician should judge the required fitness prior to registration, taking into account the results of all the relevant (i.e. pulmonary, cardiac) examinations.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix 2).
• Ability to return to the study center for adequate follow-up and vaccinations.
• Positive delayed-type hypersensitivity (DTH) skin test (induration \> 2mm after 48 hrs) against at least one positive control antigen tetanus toxoid.
• Written informed consent according to ICH-GCP.
• Subjects must have adequate organ function and adequate bone marrow reserve at screening:
• creatinine ≤ 1.5 × upper limit of normal \[ULN\] or glomerular filtration rate ≥ 50 mL/min
• alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin ≤ 1.5 × ULN
• Absolute neutrophil count ≥1.5 x 109/L, platelet count ≥100 x 109/L, and Hb ≥9.0 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test just prior to the first study drug administration on Day 1, and must be willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) or true abstinence (when this is in line with the preferred and usual lifestyle)\* during the study and for at least 12 months after the last study drug administration.
• \*True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Men must be willing to use an effective contraceptive method (e.g. condom, vasectomy) during the study and for at least 12 months after the last study drug administration.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

MeSH Terms

Conditions

Mesothelioma, Malignant

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

Central Study Contacts

Joachim Aerts, Prof

CONTACT

+31 10 703 4855; j.aerts@erasmusmc.nl

Luca Cantini

CONTACT

l.cantini@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 20, 2022
• First Posted: March 31, 2022
• Study Start: November 2, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 25, 2025

Record last verified: 2025-04

Locations

NL (1)