Treatment-naïve malignant pleural mesothelioma patients (eligible for standard chemotherapy and, in case of resectable disease, surgery) MedDRA version: 20.0 Level: LLT Classification code 10046859 Term: Vaccination System Organ Class: 100000004865 MedDRA version: 20.0 Level: PT Classification code 10059518 Term: Pleural mesothelioma malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cryopreserved Wilms' tumor 1 (WT1) mRNA-electroporated dendritic cells
Product Code: WT1 mRNA-EP DC
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Wilms' tumor 1 (WT1
Sponsors
Antwerp University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosis with histologically proven epithelial MPM. - Age: =18 years at the time of enrollment. - WHO performance status 0–1 at the time of enrollment. - Fit to undergo general anesthesia, a thoracoscopy, leukapheresis, chemotherapy, immunotherapy and (in case of resectable disease) P/D. - No history of receiving any investigational treatment within 28 days of study enrollment. - No history of intolerance to pemetrexed and/or cisplatin. - Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - Unwilling or unable to comply with the study requirements. - Prior treatment for mesothelioma. - History of other malignancy within the last five years, except for non-melanoma skin cancer and cervical carcinoma in situ or unless the investigator rationalizes otherwise. - Known proven metastases. - Known concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo. - Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the feasibility and safety of Wilms' tumor 1 mRNA-electroporated dendritic cell (DC) vaccinations in patients with malignant pleural mesothelioma (MPM) as first-line treatment combined with standard chemotherapy;Secondary Objective: Clinical objective - To assess the time to progression (TTP) and progression-free survival (PFS) after chemoimmunotherapy with or without pleurectomy/decortication (P/D) and to assess overall survival (OS) from diagnosis and start of treatment. Translational objective - To determine the in vivo systemic and local immunogenicity of WT1-targeted DC vaccination when combined with chemotherapy as treatment of MPM.;Primary end point(s): Feasibility and safety of WT1-targeted DC vaccination will be evaluated in MPM patients that undergo standard chemotherapy and, in case of resectable disease, pleurectomy/decortication. Safety will be assessed by clinical laboratory tests and adverse event reporting. - Microbiological testing (bacteria, fungi, mycoplasma, endotoxin) will be performed to assess safe DC vaccine production. - Local toxicity (e.g. skin reactions at injection site) will be reported. - Systemic toxicity will be scored according to the latest version of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC). Feasibility will be assessed based on the success of (1) leukapheresis and (2) DC vaccine preparation (production of at least 4 DC vaccines) and (3) administration of combined chemoimmunotherapy cycles within the proposed time schedule.;Timepoint(s) of evaluation of this end point: Analyses will be performed on all evaluable patients. Patients are considered evaluable if they received at least one DC vaccine. Both patient and tumor evaluation will be performed at regular visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Clinical endpoints - Clinical response analysis will be performed on all evaluable patients for disease progression and survival: (i) TTP and PFS after chemoimmunotherapy, (ii) OS from diagnosis and start of treatment. Patient follow-up is until 90 days after final DC vaccine administration or 22 months after diagnosis, whichever occurs later. Translational endpoints - Blood immunomonitoring studies will be performed prior to vaccination (baseline), after immunotherapy and following disease progression. Patients will undergo blood sample collection before leukapheresis, after the fourth vaccine and at three time points following disease progression. Tumor biopsies and surgical specimens (in case of operabel MPM) will be used for local immunological response assessment. ;Secondary end point(s): - Clinical endpoints: time to progression (TTP), progression-free survival (PFS) and overal survival (OS). Tumor assessment will be performed according to the latest modified Response Evaluation Criteria In Solid Tumors (RECIST), PET Response Criteria In Solid Tumors (PERCIST) and endpoints for cancer immunotherapy trials. - Translational endpoint: immunological responses. Systemic and local immunological response analysis will be performed to determine the in vivo immunogenicity of WT1 mRNA-electroporated DC vaccinations when combined with chemotherapy for the frontline treatment of MPM by evaluating the development of effective anti-mesothelioma immunity. | — |
Countries
Belgium
Contacts
Public ContactEva Lion
Antwerp University Hospital
Outcome results
None listed