None listed
Conditions
Brief summary
The purpose of this study is to assess if adding Lutetium-177 PSMA-597 radionuclide therapy (177Lu-PSMA) to Androgen Deprivation Therapy (ADT) and an Androgen Receptor Pathway Inhibitor (ARPI) will be more effective for treating men with prostate cancer that has spread and can be treated with hormone therapy. Who is it for? You may be eligible for this study if you are a male aged 18 or over who has prostate cancer that has spread to other parts of the body but it can be treated with hormone therapy. This means that male sex hormones, including androgens like testosterone, can be blocked or stopped to slow cancer growth. You must have evidence of metastatic disease on imaging, a reasonable general health status (ECOG 0-2), a life expectancy of at least 12 weeks, and adequate blood and organ function. Study details All participants will be receive ADT and an ARPI as you would normally get for treatment for this type of cancer, as well as an adaptive dosing of 177-Lu-PSMA. You will have PSMA PET/CT scans, blood tests, and other routine health checks to monitor your response and side effects. It is hoped that this study will help provide important information on whether adding adaptive dosing of 177Lu-PSMA to ADT and ARPI treatment will lead to better treatment responses.
Interventions
All participants will receive continuous Androgen Receptor Pathway Inhibitor (ARPI) and Androgen Deprivation Therapy (ADT) as per standard of care, in addition to adaptive-dosed study treatment: 177Lutetium-Prostate-specfic Membrane Antigen-597 ([177Lu]Lu-PSMA-597) (8.5GBq (± 10%) per dose), up to 7 (+3) doses.
Standard of Care: ADT and ARPI
The ADT and ARPI will be selected, administered and managed by the treating oncologist as per standard of care whist the participants are on the study. AD
All participants will receive continuous Androgen Receptor Pathway Inhibitor (ARPI) and Androgen Deprivation Therapy (ADT) as per standard of care, in addition to adaptive-dosed study treatment: 177Lutetium-Prostate-specfic Membrane Antigen-597 ([177Lu]Lu-PSMA-597) (8.5GBq (± 10%) per dose), up to 7 (+3) doses. Standard of Care: ADT and ARPI The ADT and ARPI will be selected, administered and managed by the treating oncologist as per standard of care whist the participants are on the study. ADT may be commenced up to 35 days prior to commencing ARPI. The first [177Lu]Lu-PSMA-597 dose will be administered 7 days (+ 1 day) after starting ARPI. Experimental intervention: [177Lu]Lu-PSMA-597 The first 3 doses of [177Lu]Lu-PSMA-597 8.5 GBq, will be administered intravenously on Day 8 (+1 day), Day 10 (+1 day) and Day 22 (+/- 3 days) after commencing ARPI (Day 1). The remaining 4 doses will be administered intravenously at 8-weekly (+/-7days) intervals unless there are treatment breaks. • The results of the week 10 PSMA PET/CT scan and PSA test will determine whether there will be a [177Lu]Lu-PSMA-597 treatment-pause prior to the next dose (Dose 4). • After dose 5, participants who have not already had a [177Lu]Lu-PSMA-597 treatment-pause, have a PSA < 1ng/mL, and no residual disease above blood-pool on the 24 week PSMA PET/CT, will be eligible for a treatment pause. • If participants are placed on a [177Lu]Lu-PSMA-597 treatment pause, ARPI + ADT will continue, and [177Lu]Lu-PSMA-597 will recommence at first confirmed PSA rise (confirmed a minimum 2 weeks apart). Only one treatment pause is allowed on trial. Following 7 doses, an additional 3 doses (7+3) of [177Lu]Lu-PSMA-597 can be given in responding participants at the discretion of the treating investigator. [177Lu]Lu-PSMA-597 will be administered intravenously. The total activity administered per dose will be recorded by measuring the residual radioactivity in the vial or in the syringe before and after administration, This will be administered according to local best practice to ensure the correct dose is administered. Strategies to assess adherence to the intervention include routine safety blood tests prior to each dose and in between doses, PSA levels, and scheduled imaging with SPECT/CT post doses. The exact dose activity prepared, dispensed and administered will be documented, including time, route and any residual activity, to confirm accurate dosing.
Sponsors
St Vincent's Health Network
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. Metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site): Synchronous metastatic hormone-sensitive prostate cancer (mHSPC) or High-volume metachronous mHSPC (high-volume is CHAARTED criteria on PSMA PET) and not suitable for radiation to the primary and/or to all sites of metastatic disease or planned for docetaxel. 2. Patients must be: a. Treatment naïve OR b. Minimally treated with: I. Less than or equal to 35 days of Luteinising Hormone-Releasing Hormone (LHRH) agonist / antagonist (ADT) or bilateral orchiectomy with or without first generation antiandrogen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation antiandrogen must be discontinued prior to start of study therapy AND II. No ARPI (abiraterone, darolutamide, apalutamide, enzalutamide) exposure III. ADT for localized disease permitted if completed less than 1 year prior to diagnosis of metastatic disease and serum testosterone normalised. 3. Evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as defines as VISION criteria within 42 days prior to Day 1. 4. Evidence of at least one metastatic bone and/or soft tissue visceral lesion documented within 42 days prior to Day 1 (PSMA PET or conventional). 5. ECOG performance status of 0 to 2. 6. Aged greater than or equal to 18 years. 7. Life expectancy greater than 12 weeks. 8. Adequate bone marrow reserve: a. White blood cell (WBC) count greater than or equal to 2.5. b. Platelets greater than or equal to 90. c. Hemoglobin greater than or equal to 90. 9. Adequate hepatic function: a. Total bilirubin less than or equal to 1.5 x the institutional upper limit of normal (ULN). For patients with known Gilbert’s Syndrome less than or equal to 3 x ULN is permitted. b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than or equal to 3.0 x UL OR less than or equal to 5.0 x ULN for patients with liver metastases. c. Albumin greater than 25 g/L 10. Adequate renal function: a. eGFR greater than 40mls/min. Participants with untreated hydronephrosis are not eligible for study participation. 11. Willing and able to comply with all study requirements (including ADT + ARPI + Lu-PSMA), and all required study assessments. 12. Signed, written, informed consent.
Exclusion criteria
1. Participants planned for taxane-based chemotherapy 2. Disease that meets the criteria for oligometastatic prostate cancer suitable for SBRT (5 or fewer sites of disease on PSMA PET or pelvic confined nodes). 3. Prior ARPI (e.g., abiraterone, darolutamide, apalutamide, enzalutamide) exposure for metastatic prostate cancer or for earlier stages of prostate cancer. 4. Participant with CNS metastases that are untreated and neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. 5. Uncontrolled intercurrent illness including but not limited to; illicit drug dependency, active/recently active malignancy or psychiatric illness that could, in investigator's opinion, potentially interfere with participation in this study or places the participant at undue risk, or complicates the interpretation of safety data 6. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression 7. Active clinically significant cardiac disease defined as: a. NYHA class ¾ congestive heart failure within 6 months prior ICF signature b. History of ECG abnormalities indicating significant risk of safety for participants in the study c. History of familial long QT syndrome or known family history of Torsades de Pointe 8. Transfusion for the sole purpose of making a participant eligible for study inclusion 9. Men in sexual relationships with partner of reproductive potential who are not willing/able to use medically acceptable forms of barrier contraception. 10. Inability to follow radiation safety precautions related to trial treatment and scans.
Outcome results
None listed