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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Virttu Biologics Limited
Sponsor:
Information provided by (Responsible Party):
Virttu Biologics Limited
ClinicalTrials.gov Identifier:
NCT01721018
First received: October 22, 2012
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Malignant Pleural Mesothelioma
Biological: HSV1716 Intra-pleural delivery
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Virttu Biologics Limited:

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 ]

Estimated Enrollment: 12
Study Start Date: October 2012
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HSV1716
Single Arm Phase I/II study.
Biological: HSV1716 Intra-pleural delivery
Other Name: Seprehvir

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721018

Locations
United Kingdom
Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust Recruiting
Sheffield, South Yorkshire, United Kingdom, S10 2SJ
Contact: Penella J Woll, MB BS PhD FRCP    +44 114 226 5235    p.j.woll@sheffield.ac.uk   
Principal Investigator: Penella J Woll, MB BS PhD FRCP         
Sponsors and Collaborators
Virttu Biologics Limited
Investigators
Principal Investigator: Penella J Woll, MB BS PhD FRCP Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital, Sheffield, S10 2SJ, UK
  More Information

No publications provided

Responsible Party: Virttu Biologics Limited
ClinicalTrials.gov Identifier: NCT01721018     History of Changes
Other Study ID Numbers: 1716-12
Study First Received: October 22, 2012
Last Updated: November 1, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Virttu Biologics Limited:
Oncolytic virus
HSV1716
Mesothelioma
MPM
Woll
Sheffield
Weston Park
Virttu
Crusade

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014