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SatisfACtion: A Phase I/II, open-label, multi-center study of [225Ac]Ac-PSMA-R2 in men with metastatic hormone sensitive prostate cancer (mHSPC) and in men with heavily pre-treated PSMA positive metastatic castration resistant prostate cancer (mCRPC) with or without prior 177Lu-labelled PSMA-targeted radioligand therapy
EU CTIS ID: 2023-507672-52-00
What this study is testing
● Primary objectives for dose escalation To characterize the safety and tolerability of 225Ac-PSMA-R2 and to the Recommended Dose for Expansion (RDE) and corresponding regimen for 225Ac-PSMA-R2 monotherapy in: Group-1: PSMA-positive mCRPC participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu). Group-2: PSMA-positive mCRPC participants not previously treated with 177Lu-labelled PSMA-targeted RLT (pre-177Lu). Group 3: PSMA-positive mHSPC participants not previously treated with 177Lu-labelled PSMA-targeted RLT (pre-177Lu). ● Primary objectives for dose expansion To evaluate the anti-tumor activity for 225Ac-PSMA-R2 in mCRPC post-177Lu and pre-177Lu treatment (naïve) and mHSPC (pre-177Lu treatment) participants.
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Ability to understand and sign an approved Informed Consent Form (ICF), and to understand and comply with all protocol requirements
- Evidence of PSMA-positive disease by 68Ga-PSMA-R11 PET/CT and eligible as determined by central reading
- Recovered or stabilized to ≤ Grade 1 from all clinically significant toxicities related to prior PCa therapy with an exception for neuropathy to ≤ Grade 2 and alopecia any grade
- A documented progressive mHSPC or mCRPC based on at least 1 of the following criteria: • Serum or plasma PSA progression defined as an increase in in PSA ≥ 25% and > 2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL. • Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. • Progression of bone disease defined as evaluable disease or new bone lesions(s) by bone scan (2 + 2 PCWG3 criteria, Scher et al 2016).
- A castrate level of serum or plasma testosterone (<50 ng/dL or < 1.7 nmol/L) for mCRPC patients at screening. Monitoring of testosterone level is not mandated for participants with mHSPC who are receiving SoC treatment.
- For mHSPC participants: treatment naïve OR minimally treated with: • Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist/antagonists 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 anti-androgen must be discontinued prior to start of study therapy or after 45 days, whichever happens first. If received, prior LHRH agonist/antagonist with or without first generation antiandrogen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy. Temporarily ADT adjuvant to EBRT in the curative setting is allowed; however, this must have been discontinued > 3 months prior to inclusion. • Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. • Prior chemotherapy is not required.
You likely can't join if
- Previous treatment with any of the following within 6 weeks of IRT cohort enrollment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.
- Transfusion for the sole purpose of eligibility into the study.
- History of CNS metastases and symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression are NOT eligible, except: • Previous therapy (surgery, radiotherapy, gamma knife) and are neurologically stable, asymptomatic, and are not receiving corticosteroids for the purposes of maintaining neurologic integrity. • Epidural disease, canal disease and prior cord involvement if those areas have been treated, are stable, and not neurologically impaired.
- Concurrent serious (as determined by investigator) medical conditions, including, but not limited to, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
- Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
- Known hypersensitivity to components of the imaging product or investigational therapy or its analogues.
See the full eligibility criteria
Who can join
- Ability to understand and sign an approved Informed Consent Form (ICF), and to understand and comply with all protocol requirements
- Evidence of PSMA-positive disease by 68Ga-PSMA-R11 PET/CT and eligible as determined by central reading
- Recovered or stabilized to ≤ Grade 1 from all clinically significant toxicities related to prior PCa therapy with an exception for neuropathy to ≤ Grade 2 and alopecia any grade
- A documented progressive mHSPC or mCRPC based on at least 1 of the following criteria: • Serum or plasma PSA progression defined as an increase in in PSA ≥ 25% and > 2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL. • Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. • Progression of bone disease defined as evaluable disease or new bone lesions(s) by bone scan (2 + 2 PCWG3 criteria, Scher et al 2016).
- A castrate level of serum or plasma testosterone (<50 ng/dL or < 1.7 nmol/L) for mCRPC patients at screening. Monitoring of testosterone level is not mandated for participants with mHSPC who are receiving SoC treatment.
- For mHSPC participants: treatment naïve OR minimally treated with: • Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist/antagonists 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 anti-androgen must be discontinued prior to start of study therapy or after 45 days, whichever happens first. If received, prior LHRH agonist/antagonist with or without first generation antiandrogen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy. Temporarily ADT adjuvant to EBRT in the curative setting is allowed; however, this must have been discontinued > 3 months prior to inclusion. • Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. • Prior chemotherapy is not required.
- For mCRPC participants: Prior orchiectomy or ongoing ADT and meet the following criteria in terms of previous 177Lu-labelled PSMA-targeted RLTs in both dose escalation and dose expansion: • Group 1 (dose escalation) and Group 1 (dose expansion): (post-ARPI, post-taxane-based chemotherapy, post-177Lu-PSMA-RLT): participants must have received previous treatment with 177Lu-labelled PSMA-targeted RLTs. • Group 2 (dose escalation) and Group 2 (dose expansion): (post ARPI, pre-177Lu-PSMA-RLT): participants must have never received previous treatment with 177Lu-labelled PSMA-targeted RLTs. Prior taxane-based chemotherapy is not required.
- Adequate organ function: • Bone marrow reserve: • White blood cell (WBC) count ≥ 3.0 x 109/L and absolute neutrophil count (ANC) ≥ 1.5 x 109/L. • Platelets ≥ 75 x 109/L. • Hemoglobin ≥ 8 g/dL (8 g/dL is equivalent to 80 g/L. • Hepatic function: • Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert’s Syndrome ≤ 3 x ULN is permitted. • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases. • Albumin > 3.0 g/dL (3.0 g/dL is equivalent to 30 g/L. • Renal function: • Creatinine clearance ≥ 60 mL/min. Note that participants with hydronephrosis or findings indicating blockage of urinary outflow are not eligible
- Human immunodeficiency virus (HIV)-infected participants who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes are eligible.
- For participants who have partners of childbearing potential, the use a method of birth control with adequate barrier protection, deemed acceptable by the Investigator during the study and for 6 months after last study drug administration.
- Adults ≥ 18 years of age
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) : ECOG 0-1 for participants in dose escalation ECOG 0-2 for participants in dose expansion
- Histological, pathological, and/or cytological confirmation of prostate cancer
- Have ≥ 1 metastatic lesion that is present on a baseline CT, Magnetic Resonance Imaging (MRI), or bone scan imaging according to baseline scan imaging as defined in protocol Section 8.3.1.
What rules you out
- Previous treatment with any of the following within 6 weeks of IRT cohort enrollment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.
- Transfusion for the sole purpose of eligibility into the study.
- History of CNS metastases and symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression are NOT eligible, except: • Previous therapy (surgery, radiotherapy, gamma knife) and are neurologically stable, asymptomatic, and are not receiving corticosteroids for the purposes of maintaining neurologic integrity. • Epidural disease, canal disease and prior cord involvement if those areas have been treated, are stable, and not neurologically impaired.
- Concurrent serious (as determined by investigator) medical conditions, including, but not limited to, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
- Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
- Known hypersensitivity to components of the imaging product or investigational therapy or its analogues.
- History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months prior to ICF signature and/or clinically active significant cardiac disease defined as any of the following: • NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3, left ventricular ejection fraction (LVEF) < 50% as determined by echocardiogram (ECHO), uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mmHg with or without antihypertensive medication. • History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study, primarily mean resting corrected QT interval (QTc) > 470 millisecond (msec), obtained from average value 3 ECG recordings taken approximately 2-3 minutes apart as per Investigator assessment and/or others such as: concomitant clinically significant cardiac arrhythmias e.g. sustained ventricular tachycardia, complete left bundle branch block, or high-grade atrioventricular (AV) block (e.g. bifascicular block). • Mobitz type II, long AT syndrome, known family history and/or current condition of Torsade de Pointes and third-degree AV block, or any factor increasing the risk of QTc prolongation(e.g. hypokalemia).
- Diagnosis of other malignancies expected to alter life expectancy or may interfere with disease assessment. Prior history of malignancy who have been disease free for more than 3 years are eligible
- A superscan as seen in the baseline bone scan
- Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 6 months after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
- Previous treatment with PSMA-targeted RLT for Group 2 and Group 3
- Any other investigational agents within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy.
- Any systemic anti-cancer therapy (e.g. other concurrent chemotherapy, radioligand therapy, immunotherapy or biological therapy including monoclonal antibodies) within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy. Patients on stable bisphosphonate or denosumab for ≥ 15 days prior to study start are not excluded (with the exception of the drugs listed on inclusion criteria #14 for mHSPC patients).
- Uncontrolled pain or incompatibility that may result in participant’s lack of ability to comply with imaging procedures
The study team makes the final eligibility decision.
Where it's taking place
- United States
- United Kingdom
- Canada
- Australia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling male, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; United Kingdom; Canada; Australia. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.