None listed
Conditions
Brief summary
The EVADE-1 study aims to assess whether a new cancer treatment, evexomostat, shows signs of anti-cancer activity in patients with advanced prostate cancer that has spread to other tissues, and to better understand the safety and tolerability of this treatment in patients with advanced prostate cancer. Who is it for? You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with metastatic castration-resistant prostate cancer and your cancer deposits/tumours also show low uptake on PSMA PET scans and/or increased uptake on FDG PET scans. You may need to ask your doctor to confirm whether your cancer meets these requirements. Study details All participants who choose to enrol in this study will be asked to attend the Princess Alexandra Hospital, Brisbane once per fortnight to receive an injection under the skin of evexomostat. If participants don't experience any severe side effects while receiving evexomostat, they will be able to continue attending fortnightly for up to 24 weeks (12 doses). Throughout the study, all participants will be asked to undergo additional PET/CT scans (4 in total), blood tests and clinical assessments to monitor their safety and any response to the treatment. It is hoped this research will determine whether regular doses of evexomostat are safe and tolerated by patients with advanced prostate cancer and to determine the effect of evexomostat on cancer activity. If the study finds that this treatment is safe and has an anti-cancer effect, a larger study to assess the treatment in a greater number of patients with advanced prostate cancer may be undertaken.
Interventions
Evexomostat (SDX-7320)
Dose: 49mg/m^2, every 14 days, up to 12 doses
Study duration: 24 weeks
Mode of delivery: Subcutaneous injection
Monitoring, administration in hospital setting
Sponsors
Queensland University of Technology
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant signed Informed Consent 2. Participant is 18 years old or older. 3. Participants enrolled must have mCRPC with at least 1 metastatic site that measures at least 10mm in diameter. 4. Participants have at least one (1) measurable progressing lesion which is PSMA low and/or FDG-avid. Low PSMA avidity on 68Ga-PSMA PET/CT is defined as SUVmax of less than 15 on at least one measurable lesion. FDG avid refers to at least one (1) PSMA-negative /FDG-positive discordant lesion. 5. Participants with de novo diagnosis of AV metastatic prostate cancer are allowed. 6. Participants who may have received previous androgen receptor pathway inhibitor(s) including apalutamide, enzalutamide, darolutamide, or abiraterone, 7. Participants must be on ADT. 8. Participant may have received a taxane-based chemotherapy and/or radiation for their advanced disease, with treatment having been at least four (4) weeks prior to first dose of evexomostat in this study 9. Participants are allowed prior PARP inhibitor treatment for BRCA1/2 mutation prostate cancer. 10. Participants are allowed to have had prior experimental antibody-drug conjugate treatment for their metastatic disease, but not for the AV disease treatment. 11. All participants should be receiving a bone-protecting agent (BPA) prior to study start 12. ECOG performance status of 2 or greater. 13. Adequate renal function: defined as Creatinine clearance of at least 50mL/ min (using either the Cockcroft-Gault equation or the CKD-EPI formula for calculation of eGFR or has chronic kidney disease (CKD) grade equal to 1.) Alternatively, a 24-hour urine test can be performed to confirm renal sufficiency. 14. Adequate liver function: a. Bilirubin less than 1.5 of the upper limit of normal (ULN) (or if bilirubin is between 1.5 and 2 times the ULN, must have a normal conjugated bilirubin) b. AST or ALT equal to 2.5 times the ULN (or equal to 5.0 times the ULN in the presence of liver metastases) 15. Adequate bone marrow function: a. Platelets equal to 120 (times 10 to the 9) per litre b. Haemoglobin of 90g per litre (no red blood cell transfusion in last 4 weeks) c. Neutrophils at least 1.5 (times 10 to the 9) per litre d. White blood cells of 2,500 cells per microlitre or greater e. Albumin of 30 gm per litre or above 16. Estimated life expectancy of at least 6 months 17. Participants must have the ability to understand and sign an approved informed consent form (ICF) and comply with all protocol requirements including agreement for intervals of PET-CT scans.
Exclusion criteria
1. Prior treatment with any PSMA-targeted radioligands/ radionuclides. 2. Participant received myelosuppressive therapy including docetaxel or cabazitaxel, within the last 4 weeks prior to planned first dose of evexomostat. 3. Participant received platinum-based or a topoisomerase inhibitor for their advanced or metastatic AVPC disease. 4. Participant is diagnosed with BRCA1/2 mutation and has not received prior treatment with a PARP inhibitor. 5. Participant has ongoing toxicities related to prior anti-cancer therapies that have not resolved to: platelets at least 120 (times 10 to the 9) per litre, ANC of 1500 per mL or greater, haemoglobin of 90g per litre or greater, and Grade 1 for other toxicities, per National Cancer Institute Common Terminology Criteria for Adverse Events. 6. Participant has an established diagnosis of type 1 diabetes mellitus or insulin dependent type 2 diabetes. 7. Participant is currently receiving any of the following medications and cannot be discontinued at least 7 days prior to the start of the treatment: a. Strong cytochrome P450 3A4 (CYP3A4) inducers or inhibitors b. Sulfonylurea-based anti-diabetic drugs (e.g., glipizide, glyburide) 8. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety 9. Participant has any other concurrent, severe and/or uncontrolled medical condition that would, in the Investigator’s judgement, contra-indicate patient participation in the clinical study (e.g., chronic active hepatitis, severe hepatic impairment, recent cardiac events, uncontrolled heart disease, additional cancerous lesions not related to their prostate cancer) 10. Patient participated in a prior investigational study within 21 days prior to the start of study treatment or within 4 half-lives of the investigational product, whichever is shorter. 11. Unsuitable for repeated PET-CT imaging.
Outcome results
None listed