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Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma. (1716-12)

Primary Purpose

Malignant Pleural Mesothelioma

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
HSV1716 Intra-pleural delivery
Sponsored by
Virttu Biologics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring Oncolytic virus, HSV1716, Mesothelioma, MPM, Woll, Sheffield, Weston Park, Virttu, Crusade

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
  • Queen Elizabeth Univeristy Hospital, NHS Greater Glasgow & Clyde Health Board

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HSV1716

Arm Description

Single Arm Phase I/II study of intra-pleural HSV1716 administration.

Outcomes

Primary Outcome Measures

Safety and tolerability of HSV1716 given by single and repeat intrapleural administration in patients with inoperable malignant pleural mesothelioma.

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.

Full Information

First Posted
October 22, 2012
Last Updated
June 8, 2017
Sponsor
Virttu Biologics Limited
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1. Study Identification

Unique Protocol Identification Number
NCT01721018
Brief Title
Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma.
Acronym
1716-12
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
November 14, 2016 (Actual)
Study Completion Date
November 14, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virttu Biologics Limited

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma
Keywords
Oncolytic virus, HSV1716, Mesothelioma, MPM, Woll, Sheffield, Weston Park, Virttu, Crusade

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HSV1716
Arm Type
Experimental
Arm Description
Single Arm Phase I/II study of intra-pleural HSV1716 administration.
Intervention Type
Biological
Intervention Name(s)
HSV1716 Intra-pleural delivery
Other Intervention Name(s)
Seprehvir
Primary Outcome Measure Information:
Title
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.
Secondary Outcome Measure Information:
Title
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).
Other Pre-specified Outcome Measures:
Title
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Penella J Woll, MB BS PhD FRCP
Organizational Affiliation
Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital, Sheffield, S10 2SJ, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
City
Sheffield
State/Province
South Yorkshire
ZIP/Postal Code
S10 2SJ
Country
United Kingdom
Facility Name
Queen Elizabeth Univeristy Hospital, NHS Greater Glasgow & Clyde Health Board
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom

12. IPD Sharing Statement

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Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma.

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