E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with unresectable malignant pleural mesothelioma |
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E.1.1.1 | Medical condition in easily understood language |
Patients with unresectable malignant pleural mesothelioma |
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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 | 10049280 |
E.1.2 | Term | Solid tumour |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the safety and tolerability of ONCOS-102 in combination with pemetrexed/cisplatin. |
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E.2.2 | Secondary objectives of the trial |
• To determine and compare tumour-specific immunological activation in the peripheral blood in the experimental group (ONCOS 102 in combination with pemetrexed/cisplatin) and the control group (pemetrexed/cisplatin). • To determine and compare immunological activation in tumour mass in the experimental group and the control group. • To determine and compare overall response rate and progression-free survival (PFS) in the experimental group and the control group. • To determine and compare overall survival (OS) in the experimental group and the control group. • To analyse the correlation between immunological activation and clinical outcome. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female ≥18 years of age. 2. Histologically confirmed unresectable (advanced) malignant pleural mesothelioma in patients who are not candidates for curative surgery and for whom therapy with pemetrexed/cisplatin is considered appropriate. o This includes patients who are naïve to chemotherapy, o and those who have already received pemetrexed/cisplatin to which their tumour initially responded, but they have relapsed after at least 6 months. 3. Measurable disease according to RECIST 1.1 by CT scan. 4. Tumour accessible to i.t. injections of ONCOS-102 and to core needle biopsy or thoracoscopy for tissue sampling and immunohistochemistry analysis. 5. ECOG/WHO performance score of 0 or 1. 6. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the Investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 7. Acceptable liver and renal functions defined as: a. Total bilirubin ≤ the upper limit of normal (ULN). b. Aspartate aminotransferase (ASAT, SGOT), alanine aminotransferase (ALAT, SGPT) ≤3.0 x ULN. c. Serum creatinine ≤1.5 x ULN 8. Acceptable haematological function defined as: a. Haemoglobin ≥10 g/dL b. Neutrophils ≥1.5 x 109/L c. Platelet count ≥100 x 109/L Patients can be transfused to meet the haemoglobin entry criteria. 9. Acceptable coagulation status: prothrombin time, international normalised ratio (INR) of blood clotting, and/or activated partial thromboplastin time within ≤1.5 x ULN. 10. All women of childbearing potential must have a negative urine or serum pregnancy test at screening and all patients must agree to use barrier contraception (i.e. condom) during study treatment and for 2 months after the last virus treatment and 6 months after the last dose of pemetrexed/cisplatin.
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E.4 | Principal exclusion criteria |
1. Receipt of oncolytic virus treatment, or vaccination with a vaccine containing live virus within 4 weeks before Day 1. 2. Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1. 3. Patients who participated in a study with an investigational drug or device within 4 weeks prior to Day 1. 4. Active bacterial, viral, or fungal infections, requiring systemic therapy. 5. Severe arrhythmia, heart failure, previous cardiac infarction, or acute inflammatory heart disease. 6. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient, if included in this study. 7. Known infection with HIV, hepatitis B, or hepatitis C. 8. Known brain metastases. 9. History of organ transplant. 10. Females who are pregnant or breast feeding. 11. Unwillingness or inability to comply with the study protocol for any reason. 12. Patients with pre-existing hearing loss or neuropathy that may worsen due to potential neurotoxicity from cisplatin. 13. Patients with a history of hypersensitivity to cisplatin or pemetrexed or cyclophosphamide (or any of its metabolites). 14. Patients who are taking phenytoin for prophylactic use. 15. History of malignant tumour, unless the patient has been without evidence of disease for at least 3 years, or the tumour was a non-melanoma skin tumour, cervical carcinoma in situ, or prostatic carcinoma in situ. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability profile of ONCOS-102 and pemetrexed/cisplatin. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This will be assessed in an ongoing basis |
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E.5.2 | Secondary end point(s) |
• Biological correlates by means of cellular and humoral immune responses in blood as well as biological changes in tumour biopsies. • Response rate and PFS according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, modified immunologically relevant RECIST (irRECIST) and PERCIST 1.0 PET criteria (PERCIST). • Overall survival. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Points 1 and 2 will be done on an ongoing basis Third point – will continue until the last treated patient has died. |
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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 | No |
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 study to assess the safety of ONCOS-102 with standard chemotherapy in mesothelioma |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | Yes |
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 trial is defined as last visit last patient |
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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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |