Comparing 6 approaches for advanced metastatic castration-resistant prostate cancer
Official title: First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
A Phase 1 Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of 225Ac-PSMA-Trillium in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
Interventions
225Ac-PSMA-Trillium (BAY3563254)
Intravenous slow injection on Day 1 of a 6 week treatment cycle.
Canadian Sites (7)
Cross Cancer Institute | Clinical Trials Unit
Edmonton, Alberta, Canada
BC Cancer | Vancouver
Vancouver, British Columbia, Canada
Juravinski Cancer Centre | Clinical Trials
Hamilton, Ontario, Canada
Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and Hematology
Toronto, Ontario, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM) | Oncology
Montreal, Quebec, Canada
Research Institute of the McGill University Health Centre | McConnell Centre for Innovative Medicine
Montreal, Quebec, Canada
Centre hospitalier universitaire de Sherbrooke (CHUS) | Oncology
Sherbrooke, Quebec, Canada
Eligibility Criteria
See who this study is looking for35 criteria
The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.
Inclusion
- +Estimated glomerular filtration rate (eGFR) \>60 mL/min/1.73 m\^2, according to the Modified Diet in Renal Disease (MDRD) abbreviated formula and serum creatinine ≤1.5 x ULN
- +Participants must have at least one PSMA-positive (prostate-specific membrane antigen) distant metastatic lesion on the screeningScreeningThe checks done before joining, to see whether a study fits.Read more → PSMA PET/CT scan using the study-designated PSMA PET tracers, as determined by the siteTrial siteA hospital or clinic where a study is actually run.Read more → InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →. For eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more → purposes, a PSMA-positive lesion must have activity greater than the liver by visual assessment of the screening PSMA PET/CT. A PSMA-positive metastatic lesion should not correspond to a normal tissue structure or benign lesion.
- +mCRPC with pathological confirmation of adenocarcinoma without small-cell or neuroendocrine features.
- +Previous treatment with at least 1 novel androgen axis drug (NAAD) (e.g., enzalutamide, apalutamide, darolutamide and/or abiraterone).
- +Prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L).
- +Prior taxane treatment:
- +Dose EscalationDose escalationLater groups receive higher amounts than earlier ones, increased step by step.Read more →: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens, or been deemed ineligible for or refused taxane therapy on consultation with their physician
- +Dose Expansion Group A: Participants must have had prior treatment with at least 1 but no more than 2 taxane regimens, in the castration-resistant setting
- +Dose Expansion Group B: Participants must not have received any taxane regimens since becoming castration-resistant
- +Dose Expansion Group C: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens, or been deemed ineligible for or refused taxane therapy on consultation with their physician
- +Prior treatment with an established Lu-PSMA therapy (i.e., dose activity and cycles comparable to approved treatments) is required for participants in Dose Expansion Group C only. More specifically, to qualify for this expansion group, participants must not have discontinued 177Lu-PSMA treatment due to intolerance.
- +Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
- +Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements within 30 days before start of study intervention, as indicated below. Note that blood transfusions (red blood cells or platelets) and administration of G-CSF or GM-CSF are prohibited within 21 days prior to screening for the below bone marrow-related parameters.
- +Hemoglobin ≥9.0 g/dL
- +Absolute neutrophil count (ANC) ≥1500/mm\^3
- +Platelet count ≥100,000/mm\^3
- +Total bilirubin ≤1.5 x the Upper limit of normal (ULN), or ≤3×ULN if the participant has a confirmed history of Gilbert's syndrome (note that participants with Gilbert's syndrome should be carefully evaluated for other liver-related disorders that may impact their suitability for this study).
- +Alanine transaminase (ALT) and Aspartate transaminase (AST) ˂2.5 x ULN (≤5 x ULN for participants with liver involvement)
- +Participants on a stable dose of anticoagulation therapy are allowed to participate if they have no sign of bleeding or clotting, and prothrombin time international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) test results are acceptable at the Investigator's discretion
- +Documented progressive mCRPC per PCWG3, and a minimum starting PSA value of 2.0 ng/mL is mandatory. Progressive mCRPC is defined as meeting at least one of the following criteria:
- +PSA progression (defined as 2 consecutive increases over a previous reference value obtained at a minimum of 1-week
- +Radiological progression in soft-tissue lesions according to PCWG3 modification of RECIST v1.1 criteria
- +Progression of bone disease (defined as ≥ 2 new bone lesions according to PCWG3 bone scan criteria)
Exclusion
- −Participants who have any of the following tumor lesions which are PSMA negative AND meet the size criteria below are excluded as determined by the siteTrial siteA hospital or clinic where a study is actually run.Read more → InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →. A PSMA-negative lesion for eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more → purposes must have activity equal to or less than the liver by visual assessment of the screeningScreeningThe checks done before joining, to see whether a study fits.Read more → PSMA PET/CT scan using the study-designated PSMA PET/CT tracers. A PSMA-negative metastatic lesion should not correspond to a normal tissue structure or benign lesion.
- −a. Any single or multiple lymph node(s) ≥2.5 cm in the short axis.
- −b. Any solid organ metastasis (e.g., lung, liver, adrenal glands, etc.) that is ≥1 cm in the short axis.
- −c. Any bone metastasis with a soft tissue component ≥ 1 cm in short axis with the soft tissue component being PSMA-negative. PSMA-negative osseous metastases without a soft tissue component do not exclude a participant.
- −d. Predominantly necrotic lesions with greater than 1 cm of enhancing tissue on contrast-enhanced computed tomography / magnetic resonance imaging (CT/MRI).
- −Prior radiopharmaceutical treatment using actinium-225.
- −Other prior radiopharmaceutical treatments:
- −Dose escalationDose escalationLater groups receive higher amounts than earlier ones, increased step by step.Read more → and Dose expansion Groups A and B: Prior treatment with a radiopharmaceutical is prohibited, with the exception of prior treatment with radium-223 dichloride more than 3 months before the start of study intervention. Note: Participants who have discontinued radium-223 dichloride treatment due to intolerance are excluded from Groups A and B.
- −Dose expansion Group C: Prior treatment with a radiopharmaceutical is prohibited with the following exceptions: Prior treatment with radium-223 dichloride more than 3 months before the start of study intervention is permitted; and prior treatment with 177Lu-PSMA more than 6 weeks before the start of study intervention is required. Note: Participants who have discontinued 177Lu-PSMA or radium-223 dichloride treatment due to intolerance are excluded from Group C.
- −Prior systemic anticancer therapy including chemotherapy, NAAD, biologic therapy, immunotherapy, or investigational therapies within 4 weeks of the start of study treatment, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study treatment is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed.
- −Prior definitive therapy (radiotherapy or surgery) completed less than 6 weeks before the start of study intervention. Note that palliative radiotherapy completed less than 6 weeks before the start of study intervention will be allowed if: (i) no more than 10% of the participants' bone marrow is irradiated, (ii) it does not encompass all potential target/measurable lesions for participants in dose expansion.
- −Toxic effects of Common Terminology Criteria for Adverse EventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → (CTCAE) v5.0 Grade ≥2 from prior anticancer therapy not yet stabilized or where significant post-treatment toxicities have been observed. Chronic toxic effects of CTCAE Grade ≤2 from prior anticancer therapy where no further resolution is expected do not require exclusionExclusion criteriaThe things that would prevent someone from taking part.Read more → with agreement between the Investigator and SponsorSponsorThe organisation responsible for the study overall.Read more → (e.g., chemotherapy-induced neuropathy, fatigue, alopecia, anorexia, etc.).
In plain language
Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.
What this study is
This study is testing a treatment for a condition.
Phase 1Phase 1The earliest stage of human testing, in a small group, focused on safety.Read more → — an early safety study in a small group, checking how it is tolerated and at what dose.
What is being given or done in this study: 225Ac-PSMA-Trillium (BAY3563254).
From the trial registry
Built from these fields:
- designModule.designInfo.primaryPurpose
- designModule.phases
- armsInterventionsModule.interventions[].name
How the study is run
Groups are assigned by the study team using set rules, rather than by chance.
This study is open-labelOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more →: everyone knows which treatment is being given, including you and the study team.
From the trial registry
Built from these fields:
- designModule.designInfo.allocation
- designModule.designInfo.maskingInfo.masking
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
There are 6 groups in this study.
From the trial registry
Built from this field:
- armsInterventionsModule.armGroups[].type
Who the study is looking for
The study lists a minimum age of 18 years, with no upper limit given.
The study is open to people of any sex.
The study does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
These are the criteria the study lists. Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part.
From the trial registry
Built from these fields:
- eligibilityModule.minimumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How big and how long
The study aims to enrol about 198 people.
The study is currently expected to finish around May 2032.
The main measurement is taken over: After the first administration of study intervention up to 42 days after the last dose of study intervention.
From the trial registry
Built from these fields:
- designModule.enrollmentInfo.count
- statusModule.completionDateStruct.date
- outcomesModule.primaryOutcomes[].timeFrame
What the study measures
Dose EscalationDose escalationLater groups receive higher amounts than earlier ones, increased step by step.Read more → and Dose Expansion: Incidence of TEAEs (including TESAEs) — measured over After the first administration of study intervention up to 42 days after the last dose of study intervention.
Dose Escalation and Dose Expansion: Severity of TEAEs (including TESAEs) — measured over After the first administration of study intervention up to 42 days after the last dose of study intervention.
Dose Escalation: Incidence of DLTs — measured over Up to and including Cycle 3 (each cycle is 42 days).
Dose Escalation and Dose Expansion: ORR by PCWG3 guideline based on InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → review — measured over Up to 18 months after end of treatment.
The study lists 2 further main measurements.
From the trial registry
Built from these fields:
- outcomesModule.primaryOutcomes[].measure
- outcomesModule.primaryOutcomes[].timeFrame
Source: NCT06217822 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.
Not medical advice. What do these terms mean?
What is being tested — in plain terms
About 225Ac-PSMA-Trillium (BAY3563254)Drug
Intravenous slow injection on Day 1 of a 6 week treatment cycle.
From the trial registry — its own words, unedited.
What a drug is here: A medicine — a chemical or small-molecule treatment — given as the thing being studied.
Read the full explanation → · in clinical review
Common questions
Answered from this trial’s registry record. Where the record doesn’t say, these answers say so rather than filling the gap.
Am I eligible for this trial?
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part. Concord cannot make that determination, and neither can any tool that has not examined you.
What the study lists: a minimum age of 18 years.
The full inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → and exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → are published on this page, exactly as the study team wrote them.
The useful next step is to bring this trial to your doctor. Answering a few questions first gives them something concrete to review.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.eligibilityCriteria
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
From the trial registry
- armsInterventionsModule.armGroups[].type
Would I know which treatment I am getting?
This study is open-labelOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more →: everyone knows which treatment is being given, including you and the study team.
Groups are assigned by the study team using set rules, rather than by chance.
From the trial registry
- designModule.designInfo.maskingInfo.masking
- designModule.designInfo.allocation
Who can join?
The study lists a minimum age of 18 years, with no upper limit given.
It is open to people of any sex.
It does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can confirm whether a particular person can take part.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How long would this take?
The study's main measurement is taken over: After the first administration of study intervention up to 42 days after the last dose of study intervention.
The study as a whole is currently expected to finish around 2032-05-28.
How long any one person takes part can differ from the study length. The study team can tell you what the schedule looks like in practice.
From the trial registry
- outcomesModule.primaryOutcomes[].timeFrame
- statusModule.completionDateStruct.date
How many people are taking part?
The study aims to enrol about 198 people.
From the trial registry
- designModule.enrollmentInfo.count
Where is this happening?
This study lists 7 locations, including: Edmonton, Alberta, Canada; Vancouver, British Columbia, Canada; Hamilton, Ontario, Canada; Toronto, Ontario, Canada; Montreal, Quebec, Canada; Sherbrooke, Quebec, Canada, and 1 more.
Sites can open and close during a study, so confirm with the team before travelling.
From the trial registry
- trial_locations
About This Trial
Researchers are looking for a better way to treat participants who have metastatic castration-resistant prostate cancer (mCRPC). mCRPC is a cancer of the prostate (male reproductive gland found below the bladder) that has spread to other parts of the body. This type of prostate cancer does not respond to hormone treatment used to lower the level of testosterone, a male sex hormone, to prevent cancer from growing. The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate cancer. It works by binding to PSMA and giving off radiation that can damage cancer cells and stop them from growing. The main purpose of this first-in-human study is to learn: * How safe is BAY3563254 in participants. * What is the recommended dose of BAY3563254 that is safe and works well that will be further tested in Part 2 of the study. * How well does BAY3563254 work in participants. To answer this, the researchers will look at: * The number and severity of medical problems including serious medical problems that participants experience after taking BAY3563254 * The number of dose-limiting toxicities (DLT) at each dose level. A DLT is a medical problem caused by a drug that is too severe to continue the use of that specific dose. * The number of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)) * The number of participants who have a decrease in the levels of PSA\* by at least 50% in their blood (also known as PSA50). PSA is a protein made by the prostate gland. High levels of PSA may indicate the presence of prostate cancer. * Participants' best response to treatment based on their PSA levels (also known as the best overall PSA response). The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose of BAY3563254 for use in the second part of the study. For this, each participant will receive one of different increasing amounts of BAY3563254. They will take BAY3563254 as an injection into a vein. All participants in the second part of the study, called dose expansion, will receive the most appropriate dose of BAY3563254 that was identified from the first part of the study. Participants in this study will take the study treatment once every 6 or 8 weeks, which is known as a treatment cycle. Each participant will have up to 4 of these treatment cycles, if the participant benefits from the treatment. Each participant will be in the study for approximately 6 years, including a screening phase of up to 30 days, 6 months of treatment depending on the participant's benefit, and a follow up phase of 60 months after the end of treatment. In addition, substudies performed during both dose escalation and dose expansion parts of the study will evaluate: * the clearance of radioactivity from the body over time * the doses of radiation that are delivered to normal organs and tumors During the study, the doctors and their study team will: * take blood and urine samples * check vital signs such as blood pressure, heart rate, and body temperature * examine heart health using electrocardiogram (ECG) * take tumor samples if required * check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and bone scan * check the tumor status using PET (positron emission tomography) * check the amount of radiation absorbed by tumors and normal organs using SPECT/CT (single-photon emission tomography and computed tomography scan) * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study. The treatment period ends with a visit in 6-12 weeks after the last BAY3563254 dose. About 6-12 weeks after the last dose and every 6 weeks thereafter, the study doctors and their team will check the participants' health and any changes in their cancer. This active follow-up period ends after 18 months. The long-term follow-up period will start after the end of the active follow-up visit and will continue for up to 60 months after the the last BAY3563254 dose. Participants will be contacted, typically by phone call or clinic visit, approximately every 12 weeks after the end of active follow-up.
Other Sites (1)
M Health Fairview Masonic Cancer Clinic - Clinics and Surgery Center
Minneapolis, Minnesota, United States
Worth passing on?
Save it to the Care Package and send it to them, or to their doctor, in one message. Whether they follow it up is theirs to decide.
Review the Care PackageThis page is for informational purposes only and does not constitute medical advice. Clinical trial eligibility can only be determined by the trial site after proper screening. Trial information is sourced from ClinicalTrials.gov and may not reflect the most current status. Always consult your healthcare provider before making decisions about clinical trial participation.