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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.


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Malignant Pleural Mesothelioma

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Trial Information

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.


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Dose limiting toxicities will be assessed at 28 days after last injection of HSV1716.

Safety Issue:

Yes

Principal Investigator

Penella J Woll, MB BS PhD FRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital, Sheffield, S10 2SJ, UK

Authority:

United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:

1716-12

NCT ID:

NCT01721018

Start Date:

October 2012

Completion Date:

April 2014

Related Keywords:

  • Malignant Pleural Mesothelioma
  • Oncolytic virus
  • HSV1716
  • Mesothelioma
  • MPM
  • Woll
  • Sheffield
  • Weston Park
  • Virttu
  • Crusade
  • Mesothelioma

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