Malignant Pleural Mesothelioma MedDRA version: 14.1 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: Herpes simplex virus lacking infected cell protein 34.5
Product Code: HSV1716
Pharmaceutical Form: Solution for injection
Sponsors
Virttu Biologics Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients with histologically proven malignant pleural mesothelioma 2.Patients with disease which is not amenable to potentially curative resection 3.Patients with pleural effusions and/or ‘trapped lung’ who (i)have an existing indwelling pleural catheter for draining of excess pleural fluid or (ii)require the insertion of an indwelling pleural catheter to drain excess pleural fluid 4.Patients with a performance status = 2 (ECOG) 5.Age of at least 18 years (at screening) 6.Ability to give written informed consent as evidenced by signature on the patient consent form, to communicate well with the investigator and to comply with the expectations of the study Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1.Patients likely to require palliative radio- or chemotherapy within 30 days 2.Any evidence of uncontrolled cardiac or respiratory disease that would be a contra-indication for virus administration 3.Any other serious medical or psychiatric disorder that would be a contra-indication for virus administration 4.Acute active infection of any kind or other severe systemic disease or medical or surgical condition that is deemed significant by the principal investigator 5. Patients with immunosuppressive disorders or on systemic steroids > 5mg prednisolone/day 6.Pregnancy: women of childbearing potential not taking adequate contraception, and women who are breast feeding 7.Previous treatment with investigational viral therapy products 8.Administration of any unlicensed or investigational product within 8 weeks of entry to the study 9.No prior or concurrent malignancy within 5 years other than basal cell carcinoma of the skin or in situ neoplasia of the cervix uteri 10.Inadequate haematological function as defined by: Haemoglobin (Hb) < 10g/dl Neutrophil Count < 1.5 x 10^9/l Platelets < 100 x 10^9/l 11.Deranged liver function tests: serum bilirubin = 1.5 x upper limit of normal reference range for laboratory; transaminases = 5 x upper limit of normal reference range 12.Patients with inadequate renal function: serum creatinine = 1.5 x upper limit of reference range for laboratory 13.Patients whose indwelling catheter is not of the type approved by the sponsor for use in the study 14.Outwith any of the inclusion criteria above or considered unsuitable for entry into the study in any other way at the discretion of the principal investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research objective is to investigate whether HSV1716 is safe and well-tolerated when administered directly into the cavity that surrounds and protects the lungs (pleural cavity) of patients with a type of cancer that originates from the linings of the pleural cavity (malignant pleural mesothelioma). The study will assess this question in the context of three groups of patients. One group will receive a single dose of HSV1716, the second group will receive two doses and the third group will receive four doses. ;Secondary Objective: The secondary question is to look for evidence of HSV1716 activity in the patients through the assessment of patient samples. In particular, the study will assess samples of pleural fluid for evidence that HSV1716 has been active in the patients tumours. Tumour measurements will also be calculated from scans (before and after treatment) to assess whether there is any correlation between HSV1716 activity and the tumour size. ;Primary end point(s): The primary objective of the study is to assess the safety and tolerability of single and repeat intrapleural administrations of HSV1716 in patients with inoperable MPM. This will be assessed by physical examination, full blood counts, biochemical profile, immunological status and adverse event reporting. ;Timepoint(s) of evaluation of this end point: For patients receiving a single dose (treatment day 1), this end point will be evaluated at follow-up visits on days 3, 5, 8, 15, 22, 29 and 57. For patients receiving two doses (treatment days 1 and 8), this end point will be evaluated on treatment days and at follow-up visits on days 10, 12, 15, 22, 29 ,36 and 57. For patients receiving four doses (treatment days 1, 8, 15 and 22), this end point will be evaluated on treatment days and at follow-up visits on days 17, 19, 22, 29, 36, 43, 50 and 57 (first 3 patients recruited) and on days 24, 26, 29, 36, 43, 50 and 57 (second group of 3 patients). Further deta | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objective is to obtain evidence of HSV716 replication and lysis of MPM cells through analysis of pleural fluid and serum samples for evidence of cell death and/or HSV1716 replication and/or changes in appropriate biomarkers (for example mesothelin, osteopontin, VEGF, M30 and M65). A subsidiary endpoint will be tumour measurement as recorded by CT scans and assessed using the modified RECIST criteria for MPM.;Timepoint(s) of evaluation of this end point: Samples will be collected for evaluation of the secondary endpoint at each scheduled visit during both the treatment phase and for 28 days following the last treatment. The schedule of visits for the patient cohorts is as set out in E5-1. For all patients, CT scans will be conducted to obtain tumour measurement at screening, day 29 and 57. | — |
Countries
United Kingdom
Outcome results
None listed