Brief Title
Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma.
Official Title
A Phase I/IIa Study of the Safety, Tolerability and Biological Effect of Single and Repeat Administration of the Selectively Replication-competent Herpes Simplex Virus HSV1716 Into the Tumor-bearing Pleural Cavity (Intrapleural) in Patients With Inoperable Malignant Pleural Mesothelioma.
Brief Summary
HSV1716, an oncolytic virus, is a mutant herpes simplex virus (HSV) type I, deleted in the
RL1 gene which encodes the protein ICP34.5.
Malignant mesothelioma is an aggressive, asbestos-related tumour of the pleural and
peritoneal cavities. It is a rare cancer which occurs in individuals who have been exposed to
asbestos, although it typically occurs decades after exposure (10-40 years later). Malignant
pleural mesothelioma forms plaques that are distributed on the surface of the pleural space
in the lung. Approximately 30% of patients require an indwelling pleural catheter for
drainage of pleural effusions. In this patient group, the indwelling catheter may be used to
facilitate loco-regional delivery of HSV1716 to the pleural space.
This study seeks to evaluate the safety and biological effects of single and multiple
administrations of HSV1716 in the treatment of malignant pleural mesothelioma.
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Safety and tolerability of HSV1716 given by single and repeat intrapleural administration in patients with inoperable malignant pleural mesothelioma.
Secondary Outcome
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.
Condition
Malignant Pleural Mesothelioma
Intervention
HSV1716 Intra-pleural delivery
Study Arms / Comparison Groups
HSV1716
Description: Single Arm Phase I/II study of intra-pleural HSV1716 administration.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
12
Start Date
October 2012
Completion Date
November 14, 2016
Primary Completion Date
November 14, 2016
Eligibility Criteria
Inclusion Criteria:
- 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:
- 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Penella J Woll, MB BS PhD FRCP, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT01721018
Organization ID
1716-12
Responsible Party
Sponsor
Study Sponsor
Virttu Biologics Limited
Study Sponsor
Penella J Woll, MB BS PhD FRCP, Principal Investigator, Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital, Sheffield, S10 2SJ, UK
Verification Date
June 2017