Specialty: Cancer, Primary sub-specialty: Lung Cancer
Conditions
Interventions
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-
Sponsors
North Bristol NHS Trust Research & Innovation Department
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 90% assessed using the trial database at end of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
England, United Kingdom
Outcome results
None listed