Condition category
Cancer
Date applied
17/06/2008
Date assigned
23/06/2008
Last edited
07/09/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Najib Rahman

ORCID ID

Contact details

Oxford Respiratory Trials Unit
University of Oxford
Oxford
OX3 0DF
United Kingdom
+44 (0)1865 225256
najib.rahman@ndm.ox.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2.1

Study information

Scientific title

Acronym

Study hypothesis

The hypothesis that forms the basis for this study is that the intrapleural administration of lipoteichoic acid-T (LTAT-T) could reduce the recurrence of malignant pleural effusion and thereby alleviate a significant cause of morbidity in metastatic solid malignancies. The mechanism by which this might occur is not fully elucidated.

Pleural infection is characterised by fibrotic obliteration of the pleural cavity (pleurodesis) during an indolent illness, and therapeutic replication of this response could produce a clinically effective pleurodesis. Gram positive pathogens are immunologically recognised by the binding of their cell wall motifs to toll-like receptors (TLRs) on the cell surface. One such motif is LTA-T, which mediates its effects through TLRs.

We hypothesised that LTA-T may be capable of inducing a therapeutically effective pleurodesis for the control of malignant pleural effusion. We have performed a dose escalation study to assess the toxicity/tolerability of LTA-T administered into the pleural space, and to produce preliminary data assessing potential pleurodesis efficacy.

The purpose of this study is to confirm the favourable safety profile of LTA-T when administered intrapleurally and to define a maximum tolerated dose.

Ethics approval

Ethics approval received from the Central Oxford Research Ethics Committee in July 2004 (ref: 04/Q1606/53).

Study design

Single centre, open label phase I toxicity trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Malignant pleural effusion

Intervention

An indwelling pleural catheter (PleurX, Denver, Colorado) was placed in the pleural effusion and the pleural space fully drained. After initial complete fluid drainage, 30 ml intra-pleural saline (saline control) was administered (day 1). The daily pleural fluid drainage was then recorded for seven days to quantify the rate of production of pleural fluid. On day seven, subjects received a single intra-pleural injection of LTA-T, according to an escalating dosing schedule. Over the next 7 days (days 7 - 14), daily pleural fluid volume drainage and pleural fluid cytology for malignant cells was performed unless pleural fluid flow ceased. On day 14, the intra-pleural catheter was flushed and closed (but left in situ) and not used again for the duration of the study unless recurrent pleural fluid caused dyspnoea.

The starting dose of LTA-T was 250 µg, with three patients planned at each dose and an increase in dose determined by side effects seen in these patients.

Intervention type

Drug

Phase

Phase I

Drug names

Lipoteichoic acid-T (LTA-T, Oncomycin™)

Primary outcome measures

Adverse events (phase I toxicity trial), measured over the entire course of the study (i.e 12 weeks).

Secondary outcome measures

1. To compare the daily production of pleural fluid over days 5 to 10 after administration
of intra-pleural LTA-T with that of the previous five days after the administration of intra-pleural saline, compared from week 1 (saline control) to week 2 (LTA-T)
2. To define the time to symptomatic pleural effusion recurrence - 'pleurodesis failure' following LTA-T administration and to estimate by comparison with the published time to recurrence after simple drainage, whether LTA-T reduces the requirement for later pleural effusion drainage, assessed at 1 month
3. To assess whether intra-pleural LTA-T alters the presence of cancer cells in drained pleural fluid and whether it induces a cellular inflammatory pleural fluid response, assessed at 2 weeks and whenever fluid available subsequently
4. To assess whether intra-pleural LTA-T influences the levels of pleural fluid cytokines known to be associated with pleural fluid production, assessed post LTAT administration (3 days)

Overall trial start date

09/11/2004

Overall trial end date

24/11/2005

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged greater than or equal to 18 years, either sex
2. Histocytologically proven malignant pleural effusion
3. A Karnofsky Performance Status of greater than or equal to 60%
4. Life expectancy of more than three months
5. Written informed consent
6. Participants were required to be willing and able to comply with the protocol
7. Participants who were at least 4 weeks from their last chemotherapy cycle

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Unknown initially as dose finding study - 14 patients recruited in total

Participant exclusion criteria

1. Serious uncontrolled intercurrent infection
2. Proven infection in this episode of pleural effusion
3. Any bleeding diathesis such that chest tube insertion would be hazardous
4. Previous surgical pleurodesis for this pleural effusion
5. Any of the following abnormal laboratory results:
5.1. Haemoglobin less than 8 g/dl (correction by transfusion allowed)
5.2. Neutrophils less than 2.0 x10^9/l
5.3. Platelet count less than 100 x 10^9/l
5.4. Serum creatinine greater than 3 x upper normal limit
5.5. Serum bilirubin greater than 5 x upper normal limit
5.6. Alanine transaminase or aspartate aminotransferase greater than 5 x upper normal limit
6. A known sensitivity to lipoteichoic acid (LTA-T)
7. If female patients were pregnant or lactating; to include all women of childbearing potential unless using a reliable and appropriate contraceptive method was used and a negative pregnancy test was confirmed
8. Any patient with organ allografts, significant cardiac disease, uncontrolled seizures, central nervous system disorders or psychiatric disability
9. Participation in any other investigational drug study within 4 weeks
10. Living too far from the study centre to attend for study follow up

Recruitment start date

09/11/2004

Recruitment end date

24/11/2005

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Oxford Respiratory Trials Unit
Oxford
OX3 0DF
United Kingdom

Sponsor information

Organisation

Oxford University (UK)

Sponsor details

Clinical Trials Research and Governance
Manor House
John Radcliffe Hospital
Headington
Oxford
OX3 9DU
United Kingdom
Heather.House@admin.ox.ac.uk

Sponsor type

University/education

Website

http://www.ox.ac.uk/

Funders

Funder type

Other

Funder name

Lunamed AG (Switzerland) - unrestricted grant

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute for Health Research (NIHR) (UK) - Biomedical Research Centre Programme (salary for Chief Investigator)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The funders had no role or influence on the study design, analysis or execution.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18775668

Publication citations

  1. Results

    Rahman NM, Davies HE, Salzberg M, Truog P, Midgely R, Kerr D, Clelland C, Hedley EL, Lee YC, Davies RJ, Use of lipoteichoic acid-T for pleurodesis in malignant pleural effusion: a phase I toxicity and dose-escalation study., Lancet Oncol., 2008, 9, 10, 946-952, doi: 10.1016/S1470-2045(08)70205-5.

Additional files

Editorial Notes