A Phase 1 interventional study of 225^Ac-PSMA-617 and 68^Ga-PSMA-11 in Prostatic Neoplasms, Castration-Resistant, sponsored by Endocyte. Active, not recruiting at 2 sites in 2 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-30.
Sponsored by Endocyte (part of Novartis) · Phase 1, Interventional, and Treatment
This is a Phase 1, open-label, international, dose escalation study to evaluate the safety of [225Ac]Ac-PSMA-617 (225Ac-PSMA-617) in men with PSMA-positive prostate cancer who have and have not had prior exposure to [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) or [177Lu]Lu-PSMA I\&T (177Lu-PSMA I\&T).
Total duration of study participation of each participant is approximately 18-24 months (12 months from enrollment to end of each treatment (EOT) plus 12 months of long-term follow up (LTFU). The total duration of the study, from first patient in (FPI) to last LTFU will be approximately 48 months.
A minimum of 3 patients will be treated in each patient group at each dose level and evaluated for the occurrence of dose-limiting toxicity (DLT) during the first 6 weeks of treatment before consideration will be given to enrolling patients into the next dose level. Dose modifications for toxicity are allowed and defined per protocol.
No more than 6 cycles of 225Ac-PSMA-617 will be administered. Patients may receive less than 6 cycles if they have disease progression, intolerable toxicity, started other anticancer therapy, or have withdrawn from treatment per participant or physician decision.
Participants may also receive supportive care therapy, as determined by the study physician, however, participants cannot receive concurrent investigational agents, cytotoxic chemotherapy, biological agents, targeted therapy, immunotherapy, other systemic radioisotopes, and hemi-body radiotherapy until completion of treatment with 225Ac-PSMA-617.
85 studies on the registry are indexed under Prostatic Neoplasms, Castration-Resistant; 28 are open to participants now.
This study's enrollment of 101 is above the median of 82 across 62 interventional studies indexed under Prostatic Neoplasms, Castration-Resistant.
Browse Prostatic Neoplasms, Castration-Resistant studies →Endocyte is the lead sponsor of 29 studies on the registry; none are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
First submitted after Endocyte became part of Novartis.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
A) One or more PSMA negative lymph nodes >2.5 cm on short axis B) Bone with PSMA-negative soft tissues component > 1 cm in short axis
Determination of disease progression on treatment prior to enrollment. Progressive disease for study entry is defined as any one or more of the following:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Men that have received prior cytotoxic chemotherapy and ARPI (e.g., abiraterone or enzalutamide), who HAVE NOT been previously treated with 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T will receive a dose of 225\^Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.
Radiation: 225^Ac-PSMA-617 · Radiation: 68^Ga-PSMA-11
Men previously treated with luteinizing hormone-releasing hormone (LHRH) agonists or orchiectomy and primary anti-androgen therapy that have not received prior cytotoxic chemotherapy or novel androgen axis drugs (e.g., abiraterone or enzalutamide) will receive a dose of 225Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.
Radiation: 225^Ac-PSMA-617 · Radiation: 68^Ga-PSMA-11
Men with progressive metastatic castration resistant prostate cancer (mCRPC) who HAVE been previously treated with 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T will receive a dose of 225Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles. Prior chemotherapy and/or novel androgen axis drugs not required.
Radiation: 225^Ac-PSMA-617 · Radiation: 68^Ga-PSMA-11
administered intravenously under the dose escalation schedule
administered intravenously at a dose of 111 - 185 MBq (3 - 5 mCi)
Recommended Phase 2 Dose (RP2D)
The RP2D for each group (Group A, B and C) is defined as the dose level that is well tolerated (i.e., at or below the MTD) and for which there may be additional findings (e.g., longer term tolerability) effecting the RP2D decision. In the case where an MTD is not identified, even at the highest dose level tested, the RP2D may be determined on the basis of data indicating adequate tolerability and therapeutic effectiveness.
Time frame: 6 weeks post Cycle 1 Day 1 (C1D1) of each dosing cohort through enrollment completion, an average of 1.5 years to determine RP2D
Percentage of Participants with treatment emergent adverse events
Safety measured by the percentage of participants with treatment emergent adverse events (events started after the first dose of study medication or events present prior to start of treatment but increased in severity based on preferred term).
Time frame: Day 1/Infusion Day up to 60 days post infusion
Overall Response Rate (ORR)
Overall Response Rate (ORR) is defined as the proportion of participants with best overall response of Complete Response (CR) or Partial Response (PR) as measured by RECIST v1.1.
Time frame: Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Duration of Response (DOR)
Duration of Response (DOR) is the time from the date of the first documented response (CR or PR) to the date of the first radiologically documented disease progression or death due to disease according to RECIST v1.1.
Time frame: Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Disease Control Rate (DCR)
Disease Control Rate (DCR) is the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1.
Time frame: Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Progression Free Survival (PFS)
Progression Free Survival (PFS) is defined as the time from Cycle 1 Day 1 (C1D1) to the first of radiographic, clinical, or prostate-specific antigen \[PSA\] progression-free survival, or censorship with events defined as follows: 1. Radiographic disease progression as determined from bone scans and contrast CT/MRI as outlined in Prostate Cancer Working Group 3 (PCWG3) and RECIST 1.1 2. Unequivocal clinical progression 3. PSA progression, defined as the date that a ≥ 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir is documented and confirmed by a second consecutive value obtained 3 or more weeks later. Rises in PSA within the first 12 weeks will be ignored. Where no decline from baseline is documented, baseline PSA is the nadir. The date of progression is date of first occurrence, not date of confirmation (PCWG3 Guidance).
Time frame: Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Percentage of Participants with Biochemical Response as measured by Prostate Specific Antigen (PSA)
Prostate-specific antigen is a glycoprotein considered as a biomarker for the response to therapy in men with prostate cancer. A 50 percent (%) decline in PSA from Baseline to the PSA level at End of Study was considered as a PSA response.
Time frame: Baseline, Days 1, 15, 29 and 43 of each Cycle (1 cycle = 8 weeks +/- 1 week), End of Treatment and every 3 months during the 12-month follow-up period
Notable Changes in Alkaline phosphatase (ALP) levels
Safety measured by the notable post-baseline changes in Alkaline phosphatase (ALP) levels compared to baseline.
Time frame: Baseline, Cycle 1 and Cycle 2 (Weekly), Cycle 3 to Cycle 6 (Bi-weekly) (1 cycle = 8 weeks +/- 1 week)
Notable Changes in Lactate dehydrogenase (LDH) levels
Safety measured by the notable post-baseline changes in Lactate dehydrogenase (LDH) levels compared to baseline.
Time frame: Baseline, Cycle 1 and Cycle 2 (Weekly), Cycle 3 to Cycle 6 (Bi-weekly) (1 cycle = 8 weeks +/- 1 week)
Change from Baseline in European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D-5L)
EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.
Time frame: Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.
Time frame: Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Change from Baseline in Brief Pain Inventory - Short Form (BPI-SF) Questionnaire: Pain Severity Score
The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 \[no pain\] to 10 \[pain as bad as you can imagine\]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.
Time frame: Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Change from Baseline in Brief Pain Inventory - Short Form (BPI-SF) Questionnaire: Pain Interference Score
The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain interference score is mean value for the 7 BPI-SF questions (questions inquiring about the extent of interference with activities by pain) where the extent is ranked from 0 (does not interfere) to 10 (completely interferes). Pain interference progression is defined as an increase in score of 50% or greater from baseline without decrease in analgesic use.
Time frame: Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Change from Baseline in Xerostomia-Related Quality of Life Scale (XeQOLS)
The XeQOLS is a validated patient reported 15-item assessment scale with 4 domains: physical functioning, pain/discomfort, personal/psychologic functioning, and social functioning. The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. A negative change from Baseline indicates an improvement of the xerostomia burden.
Time frame: Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- 1 week), End of Treatment and every 3 months during the 12-month follow-up period
Plan to share: No
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Prostatic Neoplasms, Castration-Resistant →