E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant pleural mesothelioma, epithelioid subtype (stage I-IV) |
Maligne pleuraal mesothelioma, epithelioïde subtype (stadium I-IV) |
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E.1.1.1 | Medical condition in easily understood language |
Asbestos cancer |
Asbestkanker (longvlieskanker) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046859 |
E.1.2 | Term | Vaccination |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059518 |
E.1.2 | Term | Pleural mesothelioma malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the feasibility and safety of adding atezolizumab and WT1/DC vaccination to first-line platinum/pemetrexed-based chemotherapy in patients with epithelioid MPM. |
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E.2.2 | Secondary objectives of the trial |
- To assess indicators of clinical activity of first-line platinum/pemetrexed-based chemotherapy when combined with atezolizumab and WT1/DC vaccination in epithelioid MPM patients.
- To determine the immunogenicity of atezolizumab and WT1/DC vaccination when added to first-line platinum/pemetrexed-based chemotherapy in epithelioid MPM patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent - Diagnosis with histologically proven epithelioid unresectable MPM (stage I-IV) - Aged ≥18 years at the time of signing the informed consent form - World Health Organization (WHO) performance status: grade 0-1 - Adequate hematologic and end-organ function - Negative viral serology for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) - Willing and able to comply with the study protocol, as judged by the treating physician - Women of childbearing potential must have a negative serum or urine pregnancy test at the time of screening
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E.4 | Principal exclusion criteria |
- History of another malignancy within the last three years (except for malignancies with a negligible risk of metastasis or death) - Symptomatic, untreated, or actively progressing central nervous system metastases - Active or history of autoimmune disease or immune deficiency - Severe infection within 4 weeks prior to initiation of study treatment - Prior treatment for MPM - Prior allogeneic stem cell or solid organ transplantation - Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study - Use of any investigational agent within 28 days before study enrollment - Recent treatment with systemic immunostimulatory agents or systemic immunosuppressive medication - Pregnant or breastfeeding - Any other condition, either physical or psychological, or reasonable suspicion thereof on clinical or special investigation, which contraindicates the use of atezolizumab, pemetrexed, cisplatin/carboplatin and/or WT1/DC vaccines, or may negatively affect patient compliance, or may place the patient at higher risk of potential treatment complications.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Endpoint for feasibility is the proportion of patients who completed study treatment schedule (i.e. administration of four platinum/pemetrexed-based chemotherapy cycles (CT1-4) in combination with four atezolizumab treatments (A1-4) and four WT1/DC vaccinations (V1-4)).
2. Endpoint for safety of the combination of first-line platinum/pemetrexed-based chemotherapy with atezolizumab and WT1/DC vaccination is the occurrence of AEs and SAEs during investigational treatment administration and during follow-up, as reported according to to the latest version of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC): - Proportions of patients that experienced (S)AEs possibly, probably or definitely related to pemetrexed and/or cisplatin/carboplatin and/or atezolizumab and/or WT1/DC vaccination. - Number and grade of AEs and SAEs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A first analysis will be done when 8 patients have survived 24 months after diagnosis. All available data for feasibility and safety will be evaluated.
A second analysis will be done when all patients have reached an event (death) or 24 months after diagnosis. All available data for feasibility and safety will be reevaluated.
At end of study (i.e. when all patients reached 90 days after final WT1/DC vaccination and/or atezolizumab administration or 24 months after diagnosis, whichever occurs later), final analysis for safety and feasibility will be done. If the time between the second and final analysis is less than 12 months, only final analysis will be performed. |
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E.5.2 | Secondary end point(s) |
1. Endpoints for clinical efficacy include: - Best overall response (BOR), duration of response (DOR), disease control rate (DCR), objective response rate (ORR) and progression free survival (PFS) of first-line platinum/pemetrexed-based chemotherapy in combination with atezolizumab and WT1/DC vaccination, as assessed according to the latest modified Response Evaluation Criteria In Solid Tumors (mRECIST) for malignant pleural mesothelioma and RECIST 1.1 criteria for metastatic lesions. - Overall survival (OS) from diagnosis and start of first-line treatment.
2. Endpoints for immunogenicity: - Functional WT1-specific T cell responses
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A first analysis will be done when 8 patients have survived 24 months after diagnosis. All available data for indicators of clinical efficacy and immunogenicity will be evaluated.
A second analysis will be done when all patients have reached an event (death) or 24 months after diagnosis. All available data for indicators of clinical efficacy and immunogenicity will be reevaluated.
At end of study (i.e. when all patients reached 90 days after final WT1/DC vaccination and/or atezolizumab administration or 24 months after diagnosis, whichever occurs later), final analysis for indicators of clinical efficacy and immunogenicity will be done. If the time between the second and final analysis is less than 12 months, only final analysis will be performed.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase I - feasibility/safety |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study will occur when all evaluable patients have reached 90 days after final WT1/DC vaccination and/or atezolizumab administration (i.e. end of investigational treatment) or 24 months after diagnosis, whichever occurs later. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |