None listed
Conditions
Brief summary
Brief description of the study purpose The PRELuDE study aims to test whether personalised radionuclide treatment planning using a low dose tracer scan can accurately predict tumour radiation dose and improve how ¹77Lu PSMA radioligand therapy is prescribed for people with metastatic castration resistant prostate cancer. Who is it for? You may be eligible for this study if you are aged 18 years or older with metastatic castration resistant prostate cancer who have progressive disease despite standard treatments, have PSMA positive metastatic disease on imaging, adequate organ function, and are eligible to receive 177Lu PSMA therapy. Study details All participants will receive standard 177Lu PSMA therapy at a dose of 7400–8500 MBq for two treatment cycles. Participants will receive a tracer dose of 1000 MBq 177Lu PSMA before treatment. They will then undergo serial whole body planar imaging and SPECT CT scans at approximately 4 hours, 1 day, and 3–5 days after tracer injection to measure how much radiation is delivered to tumours and normal organs. These measurements will be used to calculate the predicted biologically effective dose (BED). The BED predicted from the tracer study will be compared with the BED measured after therapeutic administration using repeat imaging at the same time points. It is hoped that this research will validate a method for prospectively predicting tumour radiation dose, enabling more precise, efficient, and personalised radioligand therapy and improving treatment outcomes for people with advanced prostate cancer.
Interventions
We propose to introduce routine clinical prospective radionuclide treatment planning for personalized precision theranostic oncology.
Standard treatment of metastatic castrate resistant prostate cancer (mCRPC) worldwide is 177Lutetium PSMA radioligand therapy administered as an arbitrary fixed activity of 7400 – 8500 Megabecquerels (MBq) for 4-6 cycles 6-8 weeks apart. Half the patients are estimated to be either undertreated or overtreated by this standard regimen. Furthermore, it has been rec
We propose to introduce routine clinical prospective radionuclide treatment planning for personalized precision theranostic oncology. Standard treatment of metastatic castrate resistant prostate cancer (mCRPC) worldwide is 177Lutetium PSMA radioligand therapy administered as an arbitrary fixed activity of 7400 – 8500 Megabecquerels (MBq) for 4-6 cycles 6-8 weeks apart. Half the patients are estimated to be either undertreated or overtreated by this standard regimen. Furthermore, it has been recently shown that two thirds of the radiation absorbed dose to tumour is delivered within the first two cycles. We aim to change practice by prescription of tumour radiation absorbed dose in Gray (Gy) prospectively in each patient in order to optimize treatment planning, analogous to routine external beam radiation oncology practice. The PRELuDE study will utilize tracer administration of 1000 MBq 177Lu-PSMA to each patient, with subsequent measurement by serial semi-quantitative, radiomic imaging measurement of individual tumour radiation absorbed dose (Gy) while taking into account radiation dose limitations for organ toxicity. Tracer studies of 1000 MBq 177Lu-PSMA have been reported in isolated studies comparing tumour of uptake of different radiopharmaceuticals in prostate cancer patients which have demonstrated their feasibility. The preliminary validation phase will be performed in 20 patients, each of whom will complete the initial two cycles of their Lu177-PSMA standard activity therapy. Each of this patient cohort will receive a prospective tracer activity of 1000 MBq and then undergo imaging with a gamma camera for 30- 60 minutes at 4 hours, 1 day and 3-5 days post injection. Image results will be semi-quantitative and qualitatively assessed from the whole body planar and SPECT-CT images acquired at the aforementioned 3 time points. The calculated BED will then be compared with that measured from repeated SPECT-CT routine radiomic imaging at 4 hours, 1 day and 3-5 days after IV administration of 7400-8500 MBq of 177Lu-PSMA therapeutic administration. Comparison of tracer predicted tumour BED and that actually delivered by therapeutic administration will be used to validate the tracer methodology. Thus determining whether predicting an effective therapeutic radiation absorbed dose prospectively in each individual patient is possible.
Sponsors
Fiona Stanley Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age. 2. Metastatic adenocarcinoma of the prostate defined by: • Documented histopathology of prostate adenocarcinoma (without any features of neuroendocrine carcinoma) OR • A clinical diagnosis based on PSA elevation and typical imaging findings for metastatic prostate cancer 3. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchidectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist). 4. Disease progression with rising PSA defined by PCWG3 criteria (sequence of 2 rising values at a minimum of 1-week intervals). 5. Disease progression after at least one taxane chemotherapy in the mCRPC setting AND at least one novel androgen receptor signaling inhibitor (in the setting of either mCSPC or mCRPC). Patients with prostate cancer that has a known BRCA mutation must have had at least one PARP inhibitor therapy. If BRCA status is unknown patients will be eligible for inclusion. 6. Imaging evidence of metastatic disease documented with standard imaging. 7. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as SUVmax >15 at a single site (regardless of lesion size) and SUV max >10 at sites of disease =10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact) without FDG discordance. Metastases subject to these criteria are for soft tissue disease (not bone metastases), and lymph node measurement taken from the short axis. 8. ECOG performance status: • 0-2. 9. Adequate renal function: • Creatinine clearance = 40mL/ min (defined by either Cockcroft-Gault formula or by nuclear medicine renal scan). 10. Adequate liver function: • Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5 - 2x ULN, must have a normal conjugated bilirubin). • AST or ALT less than or equal to 2.0 x ULN (or less than or equal to 5.0 x ULN in the presence of liver metastases). 11. Adequate bone marrow function: • Platelets greater than or equal to 100 x109/L. • Haemoglobin greater than or equal to 90g/L (no red blood cell transfusion in last 4 weeks). • Neutrophils > 1.5 x109/L. 12. Estimated life expectancy > 12 weeks. 13. Study treatment both planned and able to start within 21 days. 14. Willing and able to comply with all study requirements (additional imaging time points, tracer Lu177-PSMA injection). 15. Signed, written, informed consent.
Exclusion criteria
1. Prostate cancer with known significant sarcomatoid, or spindle cell, or neuroendocrine small cell components, or metastasis of other cancer to the prostate. 2. Site(s) of disease that are FDG-positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity OR 68Ga-PSMA SUVmax < 10 3. Prior treatment with any PSMA-targeted radiotherapy. 4. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety. 5. Pre-existing G3+ toxicities not resolved to G2 or lower before day of randomisation. 6. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse. 7. Men in sexual relationships with women of reproductive potential who are each not willing/able to use medically acceptable forms of barrier contraception.
Outcome results
None listed