Prostatic Neoplasms, Castration-ResistantPhase 1225AcPSMAI&TNCT05902247
Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy
A Phase 1 study testing Radionuclide Therapy in people with Prostatic Neoplasms, Castration-Resistant, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
225Ac-PSMA I\&T is a radiopharmaceutical for therapy of prostate cancer. PSMA is overexpressed on prostate cancer cells. Actium-225 is an alpha emitting radionuclide. When PSMA I\&T is labelled with Actium-225, it can be applied as therapy for prostate cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms, Castration-Resistant
- What is being tested?
- Radionuclide Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 29 Dec 2021to 29 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathological proven metastatic castration resistant prostate cancer. Castrationresistant disease is defined as a serum testosterone level of 50 nanogram per deciliter or lower (≤1.7 nanomol per liter) after bilateral orchiectomy or during maintenance treatment consisting of androgen-ablation therapy with a luteinizing hormone-releasing hormone agonist.
- Evidence of progressive disease, defined as 1 or more Prostate Cancer Work Grouping 3 (PCWG3) criteria: - PSA level ≥ 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart
- Progression as defined by RECIST 1.1 with PCGW3 modifications
- Progression after at least one line of chemotherapy and/or one line of nonsteroidal antiandrogen (NSAA).
- No active anti-tumor therapy, except for androgen deprivation therapy in combination with at least one androgen receptor-targeted agent
- Willing and able to undergo 2 cycles of 225Ac-PSMA I\&T therapy and 3 PET-MRI scans in 16 weeks and comply with protocol
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- Signed and dated written informed consent by the patient (or legal representative) prior to any study-specific procedures.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance-status score 0-2.
- Use of highly effective methods of contraception (female partners of male participants)
- During the trial and 6 months after completion of the study or willing to practice sexual abstinence.
Who cannot join
- Concurrent severe illness or clinically relevant trauma within 2 weeks before the administration of the investigational product that might preclude study completion or interfere with study results
- Serum hemoglobin ≤ 6.2 mmol/L, total white blood cell (WBC) count ≤ 3.5·109/L, absolute neutrophil count ≤ 1.5·109/L, platelet count ≤ 100·109/L, serum creatinine concentration ≥ 150 umol/L (≥ 1.7 mg/dL), serum albumin <30 g/L, bilirubin ≥ 1.5 x upper limit normal (ULN), aspartate transaminase (ASAT) ≥ 3 x ULN and alanine aminotransferase (ALAT) ≥ 3 x ULN (or bilirubin ≥ 3 x ULN, ASAT ≥ 5 x ULN and ALAT ≥ 5 x ULN in the case of pre-existing liver metastases at baseline)
- Concurrent bladder outflow obstruction or unmanageable urinary incontinence
- Known or expected hypersensitivity to Gallium-68, Actinium-225, PSMA I\&T, or any excipient present in 225Ac/68Ga-PSMA I\&T
- Prior administration of a radiopharmaceutical within a period corresponding to 8 halflives of the radionuclide used on such radiopharmaceutical
- Prior treatment with any radionuclide therapy
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- History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
- Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
- Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose)
- Male subjects unwilling to abstain from donating sperm during treatment and for an additional 6 months after the last dose
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus Medical Center
Rotterdam, South Holland, 3015GD
Sui wai Ling Ling, +31107033612, s.ling@erasmusmc.nl
Laurens Groenendijk, +31107033612, imaging.trialbureau@erasmusmc.nl
About this study
Official title: Phase I Dose Escalation Study to Evaluate Tolerability and Safety of 225Ac-PSMA I&T in Patients With Metastatic Prostate Cancer
225Ac-PSMA I\&T is a radiopharmaceutical for therapy of prostate cancer. PSMA is overexpressed on prostate cancer cells. Actium-225 is an alpha emitting radionuclide. When PSMA I\&T is labelled with Actium-225, it can be applied as therapy for prostate cancer.
Read the detailed description
Rationale:
225Ac-PSMA I\&T is a radiopharmaceutical for therapy of prostate cancer. PSMA is overexpressed on prostate cancer cells. Actium-225 is an alpha emitting radionuclide. When PSMA I\&T is labelled with Actium-225, it can be applied as therapy for prostate cancer.
Objective:
To evaluate the tolerability and safety of 225Ac-PSMA I\&T in patients with metastatic prostate cancer and recommend a dose for further phase 2 studies.
Study design:
A clinical prospective, single-center, single-arm, phase I dose escalation therapy study.
Study population:
Up to 30 patients with advanced metastatic castration-resistant prostate cancer (mCRPC).
Intervention:
Patients with advanced mCRPC will receive therapy with 225Ac-PSMA I\&T. The first dose-level will not exceed 8 megabecquerel (MBq), as this is reported in the literature as a save activity for treatment. A Positron Emission Tomography - Magnetic Resonance Imaging (PET-MRI) with Gallium-68-PSMA I\&T (68Ga) will be performed to calculate the precise dose-level needed and as a verification the precise dose-level will be compared with the dose-level of 8 MBq. In the first week after therapy, the PET-MRI will be repeated to observe any effects of the alpha radiation on the metastases and observe the potential changes in 68Ga-PSMA I\&T uptake. Eight weeks after the first cycle, patients will receive the second cycle of 225Ac-PSMA I\&T. If no Dose Limiting Toxicity (DLT) occurs, the dose can be increased for the next DL. If a DLT occurs, the cohort will be expanded to 6 patients. After establishing the recommended dose, an expansion cohort will be opened with a total of 12 patients.
Main study endpoints:
To investigate the safety, tolerability and biochemical effects of 225Ac-PSMA I\&T injected in patients with metastatic prostate cancer.
Primary objective:
- To assess the safety and tolerability of 225Ac-PSMA I\&T administered intravenously
Secondary objectives:
- To predict and calculate the absorbed-dose in critical organs (e.g. salivary glands, kidneys, bone marrow) by 68Ga-PSMA I\&T PET-MRI
- To evaluate the effects of the radionuclide therapy on metastases in the days after therapy using 68Ga-PSMA I\&T PET-MRI
- To evaluate the biochemical effects of 225Ac-PSMA I\&T therapy in patients with metastatic prostate cancer
- Being tested
- Radionuclide Therapy
- Keywords
- 225Ac-PSMA, Prostate cancer
- Medical subject headings
- Prostatic Neoplasms, Castration-Resistant, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radionuclide TherapyRadiation
Also called 225Ac-PSMA I&T
To evaluate the tolerability and safety of 225Ac-PSMA I\&T in patients with metastatic prostate cancer
| Study group | Role | What they receive |
|---|---|---|
| 225Ac-PSMA I&T | Experimental | 225Ac-PSMA I\&T Receives: Radiation: Radionuclide Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
Safety and tolerability assessment
Measured: 4 years
Absolute values and changes from baseline in laboratory parameters (hematology, blood chemistry and urinalysis), including assessment of shifts from baseline to abnormal values on treatment
Safety and tolerability assessment
Measured: 4 years
Absolute values and changes from baseline in vital signs & ECG parameters
Safety and tolerability assessment
Measured: 4 years
Secondary outcomes (8)
To predict and calculate the absorbed-dose in critical organs (e.g. salivary glands, kidneys, bone marrow) by 68Ga-PSMA I&T PET-MRI
Dosimetry
Measured: 4 years
Changes in SUVmax of the target lesions on PET-MRI and morphological changes evaluated on MRI
Direct effect of 225Ac-PSMA I\&T
Measured: 4 years
Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v.1.1.
Preliminary efficacy
Measured: 4 years
Percent changes from baseline in tumor size where tumor size is defined as the sum of all target lesions as measured by RECIST criteria v.1.1.
Preliminary efficacy
Measured: 4 years
Prostate Specific Antigen(PSA) response rate assessed from treatment visit 1 defined as a decrease in PSA of ≥ 50% from baseline.
Preliminary efficacy
Measured: 4 years
Percent change from baseline in PSA as a continuous endpoint by visit and maximum reduction during the study
Preliminary efficacy
Measured: 4 years
Percent change from baseline values of pain questionnaire at every treatment visit
Preliminary efficacy
Measured: 4 years
Overall Survival (OS) defined as the time from the date of first dose of 225Ac-PSMA I&T treatment to the date of death due to any cause.
Preliminary efficacy
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2023
- Study start29 Dec 2021
- Primary completion29 Dec 2025 (estimated)
- Study completion29 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostatic Neoplasms, Castration-ResistantStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A clinical prospective, single-center, single-arm, phase I dose escalation therapy study.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society
- Responsible party
- Principal investigator, Tessa Brabander, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05902247
- Sponsor's protocol ID
- NL73234.078.20
- Acronym
- 225AcPSMAI&T
- Status last verified
- Jun 2023
- First submitted
- 24 May 2023
- Last updated
- 13 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ling SW, van der Veldt AAM, Konijnenberg M, Segbers M, Hooijman E, Bruchertseifer F, Morgenstern A, de Blois E, Brabander T. Evaluation of the tolerability and safety of [225Ac]Ac-PSMA-I&T in patients with metastatic prostate cancer: a phase I dose escalation study. BMC Cancer. 2024 Jan 29;24(1):146. doi: 10.1186/s12885-024-11900-y.
PubMed 38287346
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Study to Evaluate Tolerability and Safety of 225Ac-PSMA I&T in Patients With Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT05902247
- Acronym / sponsor ID
- 225AcPSMAI&T / NL73234.078.20
- Keywords
- 225Ac-PSMA, Prostate cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Dutch Cancer Society
- Study start
- 29 Dec 2021 (actual)
- Primary completion
- 29 Dec 2025 (estimated)
- Study completion
- 29 Dec 2025 (estimated)
- First posted
- 13 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
225Ac-PSMA I\&T is a radiopharmaceutical for therapy of prostate cancer. PSMA is overexpressed on prostate cancer cells. Actium-225 is an alpha emitting radionuclide. When PSMA I\&T is labelled with Actium-225, it can be applied as therapy for prostate cancer.
Detailed description
Rationale:
225Ac-PSMA I\&T is a radiopharmaceutical for therapy of prostate cancer. PSMA is overexpressed on prostate cancer cells. Actium-225 is an alpha emitting radionuclide. When PSMA I\&T is labelled with Actium-225, it can be applied as therapy for prostate cancer.
Objective:
To evaluate the tolerability and safety of 225Ac-PSMA I\&T in patients with metastatic prostate cancer and recommend a dose for further phase 2 studies.
Study design:
A clinical prospective, single-center, single-arm, phase I dose escalation therapy study.
Study population:
Up to 30 patients with advanced metastatic castration-resistant prostate cancer (mCRPC).
Intervention:
Patients with advanced mCRPC will receive therapy with 225Ac-PSMA I\&T. The first dose-level will not exceed 8 megabecquerel (MBq), as this is reported in the literature as a save activity for treatment. A Positron Emission Tomography - Magnetic Resonance Imaging (PET-MRI) with Gallium-68-PSMA I\&T (68Ga) will be performed to calculate the precise dose-level needed and as a verification the precise dose-level will be compared with the dose-level of 8 MBq. In the first week after therapy, the PET-MRI will be repeated to observe any effects of the alpha radiation on the metastases and observe the potential changes in 68Ga-PSMA I\&T uptake. Eight weeks after the first cycle, patients will receive the second cycle of 225Ac-PSMA I\&T. If no Dose Limiting Toxicity (DLT) occurs, the dose can be increased for the next DL. If a DLT occurs, the cohort will be expanded to 6 patients. After establishing the recommended dose, an expansion cohort will be opened with a total of 12 patients.
Main study endpoints:
To investigate the safety, tolerability and biochemical effects of 225Ac-PSMA I\&T injected in patients with metastatic prostate cancer.
Primary objective:
- To assess the safety and tolerability of 225Ac-PSMA I\&T administered intravenously
Secondary objectives:
- To predict and calculate the absorbed-dose in critical organs (e.g. salivary glands, kidneys, bone marrow) by 68Ga-PSMA I\&T PET-MRI
- To evaluate the effects of the radionuclide therapy on metastases in the days after therapy using 68Ga-PSMA I\&T PET-MRI
- To evaluate the biochemical effects of 225Ac-PSMA I\&T therapy in patients with metastatic prostate cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A clinical prospective, single-center, single-arm, phase I dose escalation therapy study.
| Arm | Type | Receives |
|---|---|---|
| 225Ac-PSMA I&T | Experimental | Radiation: Radionuclide Therapy225Ac-PSMA I\&T |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histopathological proven metastatic castration resistant prostate cancer. Castrationresistant disease is defined as a serum testosterone level of 50 nanogram per deciliter or lower (≤1.7 nanomol per liter) after bilateral orchiectomy or during maintenance treatment consisting of androgen-ablation therapy with a luteinizing hormone-releasing hormone agonist.
- Evidence of progressive disease, defined as 1 or more Prostate Cancer Work Grouping 3 (PCWG3) criteria: - PSA level ≥ 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart
- Progression as defined by RECIST 1.1 with PCGW3 modifications
- Progression after at least one line of chemotherapy and/or one line of nonsteroidal antiandrogen (NSAA).
- No active anti-tumor therapy, except for androgen deprivation therapy in combination with at least one androgen receptor-targeted agent
Key exclusion criteria (10 listed)
- Concurrent severe illness or clinically relevant trauma within 2 weeks before the administration of the investigational product that might preclude study completion or interfere with study results
- Serum hemoglobin ≤ 6.2 mmol/L, total white blood cell (WBC) count ≤ 3.5·109/L, absolute neutrophil count ≤ 1.5·109/L, platelet count ≤ 100·109/L, serum creatinine concentration ≥ 150 umol/L (≥ 1.7 mg/dL), serum albumin <30 g/L, bilirubin ≥ 1.5 x upper limit normal (ULN), aspartate transaminase (ASAT) ≥ 3 x ULN and alanine aminotransferase (ALAT) ≥ 3 x ULN (or bilirubin ≥ 3 x ULN, ASAT ≥ 5 x ULN and ALAT ≥ 5 x ULN in the case of pre-existing liver metastases at baseline)
- Concurrent bladder outflow obstruction or unmanageable urinary incontinence
- Known or expected hypersensitivity to Gallium-68, Actinium-225, PSMA I\&T, or any excipient present in 225Ac/68Ga-PSMA I\&T
- Prior administration of a radiopharmaceutical within a period corresponding to 8 halflives of the radionuclide used on such radiopharmaceutical
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radionuclide TherapyAlso: 225Ac-PSMA I&TTo evaluate the tolerability and safety of 225Ac-PSMA I\&T in patients with metastatic prostate cancer | Radiation | 225Ac-PSMA I&T |
Primary outcome
Incidence and severity of Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
Time frame: 4 years
Safety and tolerability assessment
Absolute values and changes from baseline in laboratory parameters (hematology, blood chemistry and urinalysis), including assessment of shifts from baseline to abnormal values on treatment
Time frame: 4 years
Safety and tolerability assessment
Absolute values and changes from baseline in vital signs & ECG parameters
Time frame: 4 years
Safety and tolerability assessment
8 secondary outcomes
To predict and calculate the absorbed-dose in critical organs (e.g. salivary glands, kidneys, bone marrow) by 68Ga-PSMA I&T PET-MRI
Time frame: 4 years
Changes in SUVmax of the target lesions on PET-MRI and morphological changes evaluated on MRI
Time frame: 4 years
Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v.1.1.
Time frame: 4 years
Percent changes from baseline in tumor size where tumor size is defined as the sum of all target lesions as measured by RECIST criteria v.1.1.
Time frame: 4 years
Prostate Specific Antigen(PSA) response rate assessed from treatment visit 1 defined as a decrease in PSA of ≥ 50% from baseline.
Time frame: 4 years
Percent change from baseline in PSA as a continuous endpoint by visit and maximum reduction during the study
Time frame: 4 years
Percent change from baseline values of pain questionnaire at every treatment visit
Time frame: 4 years
Overall Survival (OS) defined as the time from the date of first dose of 225Ac-PSMA I&T treatment to the date of death due to any cause.
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2023.
- Derived from this study: PubMed 38287346Ling SW, van der Veldt AAM, Konijnenberg M, Segbers M, Hooijman E, Bruchertseifer F, Morgenstern A, de Blois E, Brabander T. Evaluation of the tolerability and safety of [225Ac]Ac-PSMA-I&T in patients with metastatic prostate cancer: a phase I dose escalation study. BMC Cancer. 2024 Jan 29;24(1):146. doi: 10.1186/s12885-024-11900-y.
- Individual participant dataSharing planned: No
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Prostatic Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Radionuclide Therapy in people with Prostatic Neoplasms, Castration-Resistant, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sui wai Ling (+31107033612, s.ling@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0 (time frame: 4 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05902247, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2023.