dENdritic Cell Therapy Combined With SURgEry in Mesothelioma

NCT ID: NCT05304208

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-02
• Study Completion Date: 2026-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment arm

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.

Group Type: EXPERIMENTAL

Mesopher

Intervention Type: BIOLOGICAL

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

Interventions

Mesopher

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Exclusion Criteria

• 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.
• Written informed consent according to the International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) guidelines.

• Clinical or radiological invasion of mediastinal structures (heart, aorta, spine, esophagus, etc.) and widespread chest wall invasion (stage T4). Involvement of N2 nodes. Stage IV (metastatic disease).
• Any different histology from the epithelioid MPM (as per assessed at time of diagnosis).
• Unavailability of tumor tissue after completing chemotherapy and before starting treatment with DCT.
• Subject with any concurrent medical, psychological or psychiatric disease or condition that is likely to compromise the ability to give informed consent or to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
• Use of >10 mg of prednisolone or equivalent/day (or other immunosuppressive agents) during the past 6 weeks before the first study drug administration and throughout the study. Prophylactic usage of dexamethasone (steroids) during chemotherapy is excluded from this 6-week interval. Inhaled or topical steroids, and adrenal replacement steroid ≤10 mg daily prednisone equivalent, are permit-ted in the absence of active autoimmune disease.
• Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery (other than eP/D) during the course of study treatment.
• Subject with any previous malignancy except adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the subject has been disease-free for at least 3 years.
• Prior treatment of any kind for mesothelioma, especially prophylactic track irradiation after diagnostic procedures.
• Clinically significant pleural effusion that cannot be managed with thoracentesis or pleurodesis (according to institutional practice). If pleurodesis is considered, it should be done before randomization.
• Subject with any known active serious infection, including human immunodeficiency virus (HIV), hepatitis B or C virus, or syphilis infection.
• Subject with a history of autoimmune disease, except for diabetes mellitus type I or other conditions, where patient can be eligible following discussion with medical monitor.
• Subject who has received an organ allograft.
• Serious intercurrent chronic or acute illness such as pulmonary (COPD or asthma) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for eP/D or investigational DCT.
• Pregnant women, nursing mothers, lactating women, and women of child-bearing potential who are unwilling to use effective contraceptive methods (intrauterine de-vices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) during the study and for at least 12 months after the last study drug administration.
• Men unwilling to use effective contraception for the duration of the study and for at least 12 months after the last study drug administration.
• Inadequate peripheral vein access to perform leukapheresis
• History of receiving any investigational treatment within 28 days of randomization.
• Absence of assurance of compliance with the protocol. Lack of availability for fol-low-up assessment.
• Patients with a known allergy to shellfish (may contain KLH).

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

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Joachim Aerts, MD PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Erasmus MC

Rotterdam, South Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Joachim Aerts, Prof

Role: CONTACT

j.aerts@erasmusmc.nl

+31 10 703 4855

Luca Cantini

Role: CONTACT

l.cantini@erasmusmc.nl

Facility Contacts

Anne Marie Geel

Role: primary

+31 10 7030323

Other Identifiers

76712

Identifier Type: -

Identifier Source: org_study_id