None listed
Conditions
Brief summary
The primary purpose of this trial is to evaluate the efficacy and safety of a new radionuclide therapy (177Lu-PSMA617) for advanced prostate cancer, in comparison to the standard care, cabazitaxel. 177Lu-PSMA617 is a radioactive molecule that specifically attaches to cells with high amounts of PSMA on the surface of the cells. This allows the radioactivity to be delivered mainly to the prostate cancer cells wherever they have spread, while sparing most normal tissues. Who is it for? You may be eligible to participate in this trial if you have been diagnosed with metastatic castration resistant prostate cancer for which you have previously received docetaxel. Study details All patients enrolled into this trial will be randomly allocated (by chance) to receive either 177Lu-PSMA617 or the standard care cabazitaxel chemotherapy. Patients in the 177Lu-PSMA617 arm will receive up to six six-weekly doses of 177Lu-PSMA617. Patients in the cabazitaxel arm will receive up to ten three-weekly doses of cabazitaxel. Treatment in both arms will continue until your cancer progresses, you have unmanageable side effects or until the maximum number of treatments has been reached. All patients will complete scans and questionnaires as part of this trial, up to every 3 weeks, to assess the impact of the treatment on your cancer, on your pain levels and your quality of life. It is hoped that this trial will provide further information on the risks and benefits of 177Lu-PSMA617 treatment compared with cabazitaxel in men with advanced prostate cancer.
Interventions
Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles.
The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response (as determined by physician review of SPECT/CT scans), treatment will be paused, but can be recommenced up to
Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles. The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response (as determined by physician review of SPECT/CT scans), treatment will be paused, but can be recommenced up to the maximum of 6 cycles upon progression. Adherence will be monitored by attendance at scheduled hospital treatment visits.
Sponsors
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by: • Documented histopathology of prostate adenocarcinoma OR • Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) 2. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog 3. Progressive disease with rising PSA on 3 consecutive measurements, and PSA >= 20ng/mL 4. Target or non-target lesions according to RECIST 1.1 5. Prior treatment with docetaxel 6. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax > 10 at sites of measurable disease >=10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact) 7. ECOG Performance status 0 to 2 8. Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel 9. Adequate renal function: • Cr Cl >=40mL/min (Cockcroft-Gault formula) 10. Adequate bone marrow function: • Platelets >=100 x10^9/L • Hb >=90g/L (no red blood cell transfusion in last 4 weeks) • Neutrophils > 1.5 x10^9/L 11. 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 <=2.0 x ULN (or <=5.0 x ULN in the presence of liver metastases) 12. Estimated life expectancy > 12 weeks 13. Study treatment both planned and able to start within 21 days of randomisation 14. Willing and able to comply with all study requirements, including all treatments (cabazitaxel or Lu-PSMA); and, the timing and nature of all required assessments 15. Signed, written informed consent
Exclusion criteria
1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components 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. Sjogren’s syndrome 4. Prior treatment with cabazitaxel or Lu-PSMA 5. Contraindications to the use of corticosteroid treatment 6. Active malignancy other than prostate cancer 7. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety 8. 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 9. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.
Outcome results
None listed