None listed
Conditions
Brief summary
The aim of this study is to determine the maximum safe and effective dose of a novel therapeutic ADVC001 complexed with the radio-isotope alpha-212 ([212Pb]Pb-ADVC001) for the treatment of metastatic prostate cancer. Who is it for? You may be eligible for this study if you are aged 18 years or older, have a diagnosis of metastatic adenocarcinoma of the prostate, and have received at least one cycle of androgen receptor therapy and exposure to a taxane-based chemotherapy. Study details All participants will receive treatment with four cycles of [212Pb]Pb-ADVC001. The intervention will be administered intravenously on day 1 during each 6-week cycle. Participants will be monitored for any adverse events for up to 36 weeks after commencing therapy, and will undergo imaging and blood tests for the duration of treatment to determine their response to therapy. Participants will also have blood samples collected to determine how the study drug is metabolised by the body. It is hoped that this study may help to determine the maximum dose at which [212Pb]Pb-ADVC001 is both safe and effective for the treatment of metastatic prostate cancer. This may help to direct how this novel treatment is used for individuals with metastatic prostate cancer in future.
Interventions
Treatment with a novel therapeutic ADVC001 complexed with 212-Pb (an alpha emitting radio-isotope). Patients with metastatic prostate adenocarcinoma are treated around every six weeks (for four cycles in total). There is no control group.
The starting dose is 60MBq. We are not dosing per kg; as is normal clinically in this patient group in Australia.
The cohorts will be escalated: 60 / 90 / 120/ 150 MBq
We intend 4 cohorts of three patients
All treatment is given by intravenous infusion
T
Treatment with a novel therapeutic ADVC001 complexed with 212-Pb (an alpha emitting radio-isotope). Patients with metastatic prostate adenocarcinoma are treated around every six weeks (for four cycles in total). There is no control group. The starting dose is 60MBq. We are not dosing per kg; as is normal clinically in this patient group in Australia. The cohorts will be escalated: 60 / 90 / 120/ 150 MBq We intend 4 cohorts of three patients All treatment is given by intravenous infusion The frequency is intended to be 6 weekly but it can be +/- 2 weeks At the completion of each cohort the data will be reviewed by the Safety Review Committee (SRC) and only if we have not reached a dose limiting toxicity (DLT) will the next cohort be enrolled. Under the 3+3 design if 2 of the 3 patients develop a DLT we will recruit 3 further patients at that dose level. A waiting period of 56 days will occur between cohorts. Within the cohort we will delay the patient (for a haematological DLT) and/or reduce dose at investigator discretion. The cohort will be treated (for cycle 1 and then 56 days after administration of the last patient in the dose escalation cohort (of three patients); the next cohort can be enrolled assuming the SRC are happy with the next cohort going ahead. The radiopharmaceutical dose undergoes extensive quality assurance (QA) prior to administration so we know the exact activity injected; and this is a time critical dose. The time of the infusion will be recorded. Patient measurements will be taken at cycle one (C1) over the next 12 hours until it is safe to discharge.
Sponsors
AdvanCell Isotopes Pty Ltd
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
• Male aged 18 years 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) • Patients with castration-resistant prostate cancer that have received at least one cycle of androgen receptor therapy and exposure to a taxane-based chemotherapy unless considered contraindicated by a medical oncologist or patient declines treatment • Progressive disease with rising PSA level, or new lesion(s) in the viscera or lymph nodes as per RECIST 1.1 or in bone as per Prostate Cancer Working Group 3 • Significant PSMA avidity on [68Ga]Ga-PSMA PET/CT • ECOG Performance status 0 to 2 • Adequate renal, bone and liver function (Absolute neutrophil count: greater than or equal to 2 x 109 /L , Hemoglobin: greater than or equal to 90 g/L, Platelet count: greater than or equal to 150,000 x 109/L, Serum creatinine: less than 1.5 x upper limit of normal (ULN) i.e = 125 umol/L or calculated creatinine clearance greater than or equal to 60 mL/min/1.73 m2 by Cockcroft-Gault formula, Serum total bilirubin: less than 1.5 x ULN (unless the patient has Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT: less than 1.5 x ULN in the absence of liver metastases; less than 3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria) • Estimated life expectancy greater than 12 weeks • Willing and able to comply with all study requirements, including the timing and nature of all required assessments (i.e. blood testing and scanning.) • Have provided written Informed Consent for participation in this trial
Exclusion criteria
• Prostate cancer with known significant sarcomatoid or spindle cell or neuroendocrine small cell components • Sjogren’s syndrome • ECOG status >2 • Prior treatment with radioligand therapy • Contraindications to the use of corticosteroid treatment • Active malignancy other than prostate cancer (excluding non-melanomatous skin cancers) • Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety • Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule • Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception • Severe claustrophobia that may impact the participants ability to comply with all aspects of the imaging protocol
Outcome results
None listed