Condition category
Cancer
Date applied
04/12/2017
Date assigned
05/12/2017
Last edited
14/05/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Anna Bibby

ORCID ID

http://orcid.org/0000-0001-7386-7754

Contact details

Academic Respiratory Unit
2nd floor
L&R building
Southmead Hospital
Bristol
BS10 5NB
United Kingdom

Additional identifiers

EudraCT number

2016-004727-23

ClinicalTrials.gov number

Protocol/serial number

34338

Study information

Scientific title

A Trial of Intra-pleuraL OK-432 Therapy in mesothelioma (TILT): A feasibility study using the ‘trial within a cohort’ methodology

Acronym

TILT

Study hypothesis

Is it feasible to undertake a three-armed trial within a cohort (TwiC) of intra-pleural immunotherapy in MPM and is it acceptable to participants and relatives?

Ethics approval

South West - Central Bristol, 02/05/2017, ref: 17/SW/0080

Study design

Randomised; Both; Design type: Treatment, Drug, Immunotherapy, Qualitative

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

Specialty: Cancer, Primary sub-specialty: Lung Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs

Intervention

This project investigates intra-pleural bacterial immunotherapy in MPM using the Trial within a Cohort (TwiC) methodology. Participants are recruited from an existing observational cohort (the ASSESS-meso study). 24 eligible participants are identified from the cohort, of whom 16 participants are randomly selected to be offered either OK432 or BCG. Randomisation is minimised by WHO performance status (0 vs ≥1) and tumour sub-type (epithelioid/cytological diagnosis versus non-epithelioid).

The intervention (either OK432 or BCG) is delivered intra-pleurally as a single dose via an indwelling pleural catheter. Participants are followed up at four trial visits over 12 weeks. On completion of the trial they return to standard follow up in the ASSESS-meso cohort study. Outcome data of participants in the intervention arms is compared with data from 8 control participants from ASSESS-meso. Qualitative interviews are be undertaken at the end of the trial to assess acceptability of the methodology to participants.

Intervention type

Drug

Phase

Phase II/III

Drug names

OK-432 (Picibanil)

Primary outcome measures

Feasibility is assessed using the following feasibility targets:
1. Recruitment rates to time & target >66%, i.e. 18 participants in 12 month recruitment window, or 24 participants in 18 months. This will be assessed using screening and recruitment logs at 12 months and end of trial.
2. Attrition rate of <20%, assessed from participant withdrawal forms at end of trial (nb this relates solely to attrition due to loss to follow up or participant withdrawal, it does not include attrition due to participant death)
3. Data completeness rates >90% assessed using the trial database at end of trial

Secondary outcome measures

1. Acceptability of the TwiC methodology, explored at qualitative interviews at week 12
2. Acceptability of the intervention (OK432 & BCG), assessed during qualitative interviews at week 12, and by reviewing randomisation logs at the end of trial to determine how many participants were offered the intervention but declined to receive it
3. Safety of intra-pleural OK432 or BCG assessed continuously throughout the trial using patient notes and AE reporting, and tabulated at end of trial
4. Tumour response rates, measured on CT chest at baseline and week 12 using modified RECIST criteria
5. Progression-free survival rates at week 12, measured using modified RECIST criteria on CT chest alongside survival status obtained from patient notes
6. Patient-reported chest pain and breathlessness, measured on visual analogue scales (VAS) at baseline, week 3, week 6 and week 12
7. Patient-reported quality of life, measured using the EQ-5D-5L health questionnaire at baseline, week 3, week 6 and week 12
8. Pleurodesis rates, defined as pleural fluid drainage of less than 50ml on 3 consecutive occasions, with <25% opacification on CXR or <250ml pleural fluid on thoracic ultrasound scanning (TUS) assessed from IPC drainage diaries baseline, week 3, week 6 and week 12
9. Biomarker response, assessed using serum mesothelin blood tests at baseline, week 3, week 6 and week 12
10. Immunological response (BCG arm only) assessed using Mantoux skin testing at baseline and week 6

Overall trial start date

01/09/2016

Overall trial end date

31/03/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histological or cytological diagnosis of MPM
2. Enrolled in ASSESS-meso cohort study and has given consent to undergo randomisation for future trials
3. IPC in situ that has drained more than 50ml of fluid on previous 3 drainages OR willing to have an IPC and has a pleural effusion suitable for IPC insertion
4. No chemotherapy in preceding 4 weeks and none planned in subsequent 4 weeks
5. Performance status ≤2, or PS 3 and felt clinically suitable for trial
6. Predicted survival ≥12 weeks from enrolment
7. Able to give written informed consent & meet trial requirements

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 24; UK Sample Size: 24

Participant exclusion criteria

1. No indwelling pleural catheter (IPC) in situ, and has contra-indication to IPC insertion
2. Clinico-radiological diagnosis of mesothelioma
3. Trapped lung with < 50% pleural apposition on x-ray
4. Moderately heavy or heavily loculated pleural effusion
5. Known immunodeficiency or immuno-suppressive medication
6. Intercurrent infection (pleural or elsewhere) or clinical signs of sepsis
7. Known sensitivity or allergy to OK432 or penicillin
8. Previous treatment with immunotherapy
9. Currently enrolled in any other interventional clinical trial
10. Brain metastases or CNS involvement of mesothelioma
11. Pregnancy or lactation, current or planned during the study period
12. Age < 18
13. Any other factor that, in the opinion of the Chief Investigator, would mean participation in the study would be contraindicated

Recruitment start date

02/01/2018

Recruitment end date

05/01/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Southmead Hospital
North Bristol NHS Trust
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Churchill Hospital
Oxford University Hospitals NHS foundation Trust
Oxford
OX3 7LE
United Kingdom

Sponsor information

Organisation

North Bristol NHS Trust Research & Innovation Department

Sponsor details

3rd Floor L&R Building
Southmead Hospital
Southmead Road
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Publication of two papers in high-impact peer-reviewed journals is planned for March 2020, one reporting the quantitative trial results, and one reporting the qualitative research findings. Plan publication of the protocol in a peer-reviewed journal.

IPD sharing statement:
Anonymised individual patient data can be made available for secondary research (please contact anna.bibby@bristol.ac.uk) once the study has been completed and final trial report published (likely March 2020), conditional on assurance from the secondary researcher that the proposed use of the data is compliant with the MRC Policy on Data Preservation and Sharing regarding scientific quality, ethical requirements and value for money.

Intention to publish date

31/03/2020

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

14/05/2018: Internal review. 16/01/2018: Internal review.