None listed
Conditions
Brief summary
Immunotherapy targeting immune checkpoint molecules (cell markers) is a new treatment option for patients with mesothelioma. The purpose of this study is to use a novel positron emission tomography (PET) imaging tracer to identify tumour cells that are expressing a specific marker (PD-L1) on mesothelioma tumours using imaging. A new non-invasive method of imaging PD-L1 in people with mesothelioma may allow clinicians to better guide immunotherapy treatment that is personalised for each patient. Who is it for? You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with either pleural or peritoneal mesothelioma and you have not yet undergone any immune checkpoint therapy (immunotherapy). Study details This study will enrol participants into one of two stages. Participants enrolled in Stage 1 of this study will be asked to undergo 4 imaging scans in total over a 7 day period. On the first day, participants will undergo two different but similar CT scans. Each scan will involve injection of a specific tracer/dye into a vein 20 minutes prior to the scan being undertaken. Each scan is anticipated to take up to an hour, the total time needed to complete both scans is not anticipated to take more than 3 hours. Participants will then be asked to return 3 days and then between 5-7 days after the first scans to undergo two further scans. These follow-up scans are anticipated to take up to an hour. Participants who choose to enrol in Stage 2 of this study will also be asked to undergo 4 imaging scans in total but this will occur over a longer period of time. Prior to their scheduled anti-cancer systemic therapy, participants will undergo two different but similar CT scans. Each scan will involve injection of a specific tracer/dye into a vein 20 minutes prior to the scan being undertaken. Each scan is anticipated to take up to an hour, the total time needed to complete both scans is not anticipated to take more than 3 hours. Participants will then either receive immunotherapy alone or immunotherapy with chemotherapy. Six weeks after the commencement of systemic therapy, participants will undergo another two scans. A follow-up appointment to discuss any adverse events, the cancer response and a general physical examination of health will be arranged at the next appointment in line with standard of care. It is hoped this research will determine whether this new imaging method is able to accurately identify tumour cells that are expressing PD-L1 and whether this imaging is able to show differences in cell expression over the course of immunotherapy treatment for patients with mesothelioma. Any advance in predicting treatment outcomes would benefit mesothelioma patients by avoiding unnecessary toxicity and better personalising therapy. People in whom the new PET imaging demonstrates a very low chance of immunotherapy response may choose to participate in clinical trials or to be trated with chemotherapy.
Interventions
Meso ImmunuPET imaging using an 89-Zirconium-Durvalumab tracer (89Zr-durva)
All scans will be performed face to face by physicists from the Sir Charles Gairdner Hospital Nuclear Medicine Department or the Peter MacCallum Cancer Centre. Patient consent and registration may occur face to face or via telephone. This will be provided to the individual patient.
If the doctor confirms eligibility and a PICF is signed, the patient will be registered to this study. The patient’s personal details, me
Meso ImmunuPET imaging using an 89-Zirconium-Durvalumab tracer (89Zr-durva) All scans will be performed face to face by physicists from the Sir Charles Gairdner Hospital Nuclear Medicine Department or the Peter MacCallum Cancer Centre. Patient consent and registration may occur face to face or via telephone. This will be provided to the individual patient. If the doctor confirms eligibility and a PICF is signed, the patient will be registered to this study. The patient’s personal details, medical history, any concomitant medications, the mesothelioma diagnosis and current cancer status will be noted. For stage 1 of the study, the patient will undergo an (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan and an 89Zr-durva PET/CT scan. As part of this safety study, a follow up imaging scan 3 and 5 to 7 days after the first 89Zr-durva PET/CT scan will be performed and vitals and adverse events will be monitored. For stage 2 of the study, patients must be commencing anti-cancer immunotherapy. Before any anti-cancer systemic therapy, the patient will undergo a baseline FDG PET/CT scan and 89Zr-durva PET/CT scan. The prescribed systemic therapy will be either immunotherapy alone or immunotherapy with chemotherapy. Six weeks (+/- 5 days) after the commencement of systemic therapy, a second FDG PET/CT scan and 89Zr-durva PET/CT scan will be performed. A follow-up appointment to discuss any adverse events, the cancer response and a general physical examination of health will be arranged. All scans will be performed according to current departmental guidelines on an integrated PET/CT scanner and reported by a qualified PET physician. Baseline scans will be performed prior to the commencement of systemic therapy. 89Zr-durva (the prescribed dose of 89Zr-durva administered to each patient will be 0.88MBq/kg up to a maximum of 74MBq). For stage 1 of the study, the emission scan will be initiated at day 0, 3 and 5 ± 2 day after injection of 89Zr-durva and the precise timing of scan initiation should be recorded. Timing of the subsequent scan will be the same as that used for the baseline scan (± 10% of the elapsed time post injection). Following current practice, intravenous contrast will not be administered. PET CT scans will be acquired as per local low dose CT protocols and duration of emission imaging will be determined locally. Images will be reconstructed using standard software provided with the cameras and displayed for analysis on dedicated image analysis software. It is anticipated that a patient will be imaged on the same camera and reconstruction parameters will be consistent across all visits. FDG PET/CT injection and scan will take 1-2 hours. 89Zr-durva PET/CT scans will take approximately 1 hour. No other contrast dyes or markers will b e adminsitered. Stage 1 Before treatment, patients will undergo an FDG PET/CT injection and scan and a 89Zr-durva PET/CT injection and scan on the same day. There is no further injection from then. This is a study for biodistribution and safety, so the patient will also be asked to get a follow-up scan at day 3 and day 5-7 after the first 89Zr-durva PET/CT scan. Therefore patients will receive a total of 4 scans. There is no follow-up scan post treatment in this stage of the study. Stage 2 Stage 2 will begin once 5 patients have been recruited for Stage 1 of the study (when we have seen biodistribution results that help inform optimised day of scan). Baseline FDG PET/CT and 89Zr-durva PET/CT injection and scan will be performed on the same day. Subsequent 89Zr-durva PET/CT scans will be performed on the day optimised by Stage 1. FDG and 89Zr-durva PET/CT scans post treatment will also be conducted on the same day. Follow-up appointments will be apart of patient standard of care. A scan worksheet will be developed separate to the protocol to keep track of scan session attendance and checklist and radiological reports will be stored in a secure XNAT system.
Sponsors
The University of Western Australia
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for inclusion in Stage 1, patient must satisfy ALL of the following: • Written informed consent • Able to undergo study procedures • Life expectancy > 12 weeks • Minimum age 18 years, no maximum age • Body weight > 30kg • Patients with histologically or cytologically confirmed mesothelioma, pleural or peritoneal • No prior immune checkpoint therapy • Estimated glomerular filtration rate (eGFR) > 60ml/min • An Eastern Cooperative Group Oncology Group (ECOG) performance score of 0-2 • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. • Male or female patients of reproductive potential who are employing an effective method of birth control To be eligible for inclusion in Stage 2, patient must satisfy ALL of the following: • Written informed consent • Minimum age > 18, no maximum age • Body weight > 30kg • Histologically confirmed malignant pleural mesothelioma • Planned to undergo systemic treatment incorporating checkpoint blockade for their disease • eGFR > 60ml/min • ECOG performance status 0-1 • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. • Male or female patients of reproductive potential who are employing an effective method of birth control
Exclusion criteria
Patients will be excluded from the Stage 1 study if ANY of the following apply: • Currently receiving chemotherapy or radiotherapy • Pregnant or breastfeeding at the time of study enrolment • Inadequate English language to complete study outcome measures • Geographically inaccessible for follow-up • Less than 18 years of age • Prior immune checkpoint inhibitor therapy • Known sensitivity or allergy to any study agents • Any serious medical condition which the investigator feels may interfere with the procedures or evaluations of the study • Patients unwilling or unable to comply with protocol or with a history of non-compliance or inability to grant informed consent • Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control Patients will be excluded from the Stage 2 study if ANY of the following apply: • Any previous therapy or condition that precludes treatment of mesothelioma with checkpoint blockade therapy • Prior immune checkpoint inhibitor therapy • Recent major surgery within 4 weeks prior to entry into the study that would prevent administration of study drug • Another concurrent active malignancy which may have the potential to confound imaging findings. • Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients • Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results
Outcome results
None listed