In this multicenter phase I/II trial, dendritic cells (DCs) loaded with the mesothelioma-associated tumor antigen WT1 will be used in conjunction with conventional chemotherapy for the frontline treatment of malignant pleural mesothelioma (MPM). The general objective is to provide the first-in-human experimental demonstration that the combination of platinum/pemetrexed-based chemotherapy with WT1-targeted DC vaccination is feasible and safe and enables the induction of both systemic and in situ mesothelioma-specific immune responses in patients with MPM.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
Biological: dendritic cell vaccination plus chemotherapy
Primary outcomes (2)
measure
Number of MPM patients with feasible and safe DC vaccine production
timeFrame
Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)
description
Production of autologous DC vaccines from newly diagnosed MPM patients will be evaluated for:
1. Feasibility, assessed by success of leukapheresis and production of sufficient (i.e. at least 4 vaccines) and qualified (phenotypic and functional requirements) vaccines.
2. Safety, assessed by microbiological testing (bacteria, yeast, fungi, mycoplasma, endotoxin) of the DC vaccines.
measure
Number of patients receiving investigational DC vaccine administration combined with standard of care chemotherapy within the proposed time frame
Eligibility
Eligibility (as posted)
Sex
All
Minimum age
18 Years
Show eligibility criteria text
Inclusion Criteria:
* Diagnosis with histologically proven epithelial
* Aged ≥ 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 P/D (in case of resectable disease)
* No history of receiving any investigational treatment within 28 days of study enrollment
* No history of intolerance to pemetrexed and/or cisplatin
* Women of child bearing potential must have negative serum or urine pregnancy test at the time of screening. They should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least hundred days after the last study treatment. If pregnancy does occur within this time period, the Principal investigator must be informed as soon as possible. Female subjects who are breastfeeding should discontinue nursing prior to the first dose of study treatment and until hundred days after the last study treatment
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discusses with the patient before registration in the trial. Absence of any other inability or unwillingness to comply with the requirements of the protocol as assessed by the investigator
* Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations
Exclusion Criteria:
* Unwilling or unable to comply with the study requirements
* Prior treatment for MPM
* History of another malignancy within the last five years (except for carcinoma in situ of the cervix, basal cell or spinocellular carcinoma of the skin 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 breast-feeding
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timeFrame
After the chemoimmunotherapy treatment (+/- 15 weeks after entry to trial)
description
Administration of 4 autologous DC vaccines combined with four 3-weekly platinum/pemetrexed-based chemotherapy cycles will be evaluated for:
1. Feasibility, assessed by successful administration of DC vaccines and prior to surgery in case of resectable disease.
2. Safety, assessed by local (e.g. skin reactions at injection site) and systemic (toxicity grading according to the latest version of the CTCAE and CTC ) tolerability to the treatment.
Secondary outcomes (4)
measure
Objective clinical responses by tumor evaluation (clinical efficacy)
timeFrame
Through study completion, at least after 4 DC vaccinations, prior to surgery (in case of resectable disease) + three months after the last intervention and within every 12 months during follow-up
description
Objective clinical responses to the chemoimmunotherapy and, in case of resectable disease, after surgery as compared to baseline tumor evaluation prior to treatment (i.e. at diagnosis), will be evaluated with:
1. radiographic assessments (CT imaging) of the tumor response using the modified RECIST criteria.
2. FDG-PET assessments of the tumor response using the PERCIST criteria.
Patients will be followed for disease progression; time to progression (TTP) and progression-free survival (PFS).
measure
Overall survival (clinical efficacy)
timeFrame
Through study completion, an average of 1 year
description
Patients will be followed for survival, from diagnosis and from start of treatment, for which the accurate date and reason of death (cancer-related or non-related) will be recorded for every patient.
measure
Systemic immunogenicity
timeFrame
After the fourth DC vaccine (i.e. post chemoimmunotherapy, prior to surgery in case of resectable disease)
description
Systemic immunogenicity will be evaluated by:
1. Detection of WT1-specific T cell immunity and innate immunity in peripheral blood.
2. Response to delayed-type hypersensitivity (DTH) skin testing to the DC vaccine.
measure
Local immunogenicity
timeFrame
Upon surgery (P/D)
description
Local immunogenicity will be evaluated by detection of immune profile in tumor biopsies and/or pleurectomy specimens (in case of resectable disease).
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