Primary Outcome Measures:
- Safety and tolerability of HSV1716 given by single and repeat intrapleural administration in patients with inoperable malignant pleural mesothelioma. [ Time Frame: Dose limiting toxicities will be assessed at 28 days after last injection of HSV1716. ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Obtain evidence of HSV1716 replication and lysis of malignant pleural mesothelioma cells through analysis of pleural fluid and serum samples for evidence of cell death and/or HSV1716 replication and/or changes in appropriate biomarkers. [ Time Frame: Samples will be collected at each outpatient visit up to day 29 (Part A), or day 50 (Part B). ] [ Designated as safety issue: No ]
Other Outcome Measures:
- Tumour measurement as recorded by CT scans and assessed using the modified Response Criteria in Solid Tumors (RECIST) for MPM. [ Time Frame: CT scans at Baseline, day 29 and day 57. ] [ Designated as safety issue: No ]
Detailed Description:
The study will be conducted in two parts. PART A is a single centre, single dose design, open label. Patients with inoperable malignant pleural mesothelioma will receive a single dose of HSV1716 by intrapleural administration. Delivery will be by direct administration via an indwelling catheter into the pleural cavity. PART B is a single centre, repeat dose design, open label. Two groups of three patients with inoperable malignant pleural mesothelioma will receive 2 (group 1) or 4 (group 2) single doses of HSV1716 at weekly intervals. Administration will be via an indwelling catheter into the pleural cavity.
Eligibility Criteria
- Inclusion Criteria:
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- Patients with histologically proven malignant pleural mesothelioma
- Patients with disease which is not amenable to potentially curative resection
- Patients with pleural effusions and/or ‘trapped lung’ who (i) have an existing indwelling pleural catheter for draining of excess pleural fluid or (ii) who require the insertion of an indwelling pleural catheter to drain excess pleural fluid
- Patients with a performance status ≤ 2 (ECOG)
- Age of ≥ 18 years (at screening)
- 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
- Exclusion Criteria:
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- Patients likely to require palliative radio- or chemotherapy within 30 days
- Any evidence of uncontrolled cardiac or respiratory disease that would be a contra-indication for virus administration
- Any other serious medical or psychiatric disorder that would be a contra-indication for virus administration
- Acute active infection of any kind or other severe systemic disease or medical or surgical condition that is deemed significant by the principal investigator
- Patients with immunosuppressive disorders or on systemic steroids > 5mg prednisolone/day
- Pregnancy: women of childbearing potential not taking adequate contraception, and women who are breast feeding
- Previous treatment with investigational viral therapy products
- Administration of any unlicensed or investigational product within 8 weeks of entry to the study
- No prior or concurrent malignancy within 5 years other than basal cell carcinoma of the skin or in situ neoplasia of the cervix uteri
- Inadequate haematological function as defined by:
Haemoglobin (Hb) < 10g/dl, Neutrophil Count < 1.5 x 10e9/l, Platelets < 100 x 10e9/l
- 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
- Patients with inadequate renal function: serum creatinine ≥ 1.5 x upper limit of reference range for laboratory
- Patients whose indwelling catheter is not of the type approved by the sponsor for use in the study
- 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
