E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant pleural mesothelioma |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the outside lining of the lung |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059518 |
E.1.2 | Term | Pleural mesothelioma malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this study is to answer the question “Is it possible (feasible) to undertake a trial within a cohort to investigate the effect of OK432, administered directly into the chest in people with mesothelioma, and is it acceptable to patients and relatives?”
This research will determine whether a full-scale version of the trial is possible. If it is, the results of this research will inform the design of the subsequent full-scale trial.
The long-term goal is to determine whether OK432 is an effective treatment for mesothelioma, and whether the trial within a cohort design is appropriate for mesothelioma trials.
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to gather preliminary (exploratory) information on the clinical effect of OK432 administered into the lung lining in people with mesothelioma. This information will be used to decide what the primary outcome measure of the subsequent full-scale trial should be. The results for the chosen outcome measure from this research will be used to calculate the sample size needed for the subsequent trial. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To participate in TILT patients must meet all of the following inclusion criteria: • Histological or cytological diagnosis of mesothelioma • Enrolled in ASSESS-meso and has given consent to be considered for and be randomly selected for future trials • Indwelling pleural catheter (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 • No chemotherapy in preceding 4 weeks and none planned in subsequent 4 weeks • Performance status ≤2, or PS 3 and felt clinically suitable for trial • Predicted survival ≥12 weeks from enrolment • Able to give written informed consent & meet trial requirements
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E.4 | Principal exclusion criteria |
To be eligible for TILT, participants must have none of the following exclusion criteria: • No indwelling pleural catheter (IPC) in situ, and has contra-indication to IPC insertion • Clinico-radiological diagnosis of mesothelioma • Trapped lung with <50% pleural apposition on x-ray • Moderately heavy or heavily loculated pleural effusion • Known immunodeficiency or immuno-suppressive medication • Intercurrent infection (pleural or elsewhere) or clinical signs of sepsis • Known sensitivity or allergy to OK432 or penicillin • Previous treatment with immunotherapy • Currently enrolled in any other interventional clinical trial • Brain metastases or CNS involvement of mesothelioma • Pregnancy or lactation, current or planned during the study period • Age <18 • Any other factor that, in the opinion of the Chief Investigator, would mean participation in the study would be contraindicated
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E.5 End points |
E.5.1 | Primary end point(s) |
Feasibility. This assessment will be based on: • Screening, eligibility and recruitment rates to TILT • Feasibility of identifying 45 eligible participants in a 12 month period • Acceptance rates for intra-pleural OK-432 following random selection • Collection of data on participants who declined to receive OK-432 when offered it • Collection of data on participants within ASSESS-meso who declined to be considered for future trials • Attrition rates and data completeness rates • Acceptability of trial processes and design to participants and their relatives, assessed qualitatively.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This will be evaluated at the end of trial - i.e. 12 weeks after the final participant has enrolled. |
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E.5.2 | Secondary end point(s) |
Secondary outcome measures will collect exploratory data on the clinical efficacy of OK-432. This data will be used to decide the primary outcome for the subsequent full-scale trial, and to estimate the variance of the chosen outcome for a sample-size calculation. Potential outcomes include:
• Tumour response, based on CT appearances • Overall survival (OS), defined as time between date of diagnosis with MPM to date of death, censored 12 weeks after the final trial visit of the final participant • Progression-free survival rates • Patient-reported chest pain and breathlessness, measured on visual analogue scales • Patient-reported quality of life, measured using the EQ-5D-5L health questionnaire • 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) • Time to pleurodesis, calculated from baseline assessment to date of pleurodesis • Biomarker response assessed using serial serum and pleural mesothelin levels. • Pleural fluid cytokine response, including VEG-F and TNF-α
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumour response will be assessed at baseline and 12 weeks Overall survival will be assessed at the end of trial (last visit of last participant) Progression free survival rates will be assessed at 12 weeks Patient reported outcomes and QoL will be assessed at baseline, week 2, week 5 and week 12 Daily VAS scores will be collected for 21 days between week 2 and week 5 Pleurodesis rates will be assessed at week 5 and week 12 Biomarkers and pleural fluid cytokines will be measured at week 0, week 2, week 5 and week 12.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |