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Metastatic Castration-resistant Prostate CancerPhase 1/2ACT-RESoLUTENCT07414940

ACTinium in Castrate-RESistant Prostate Cancer After LUTEtium

A Phase 1/2 study testing Actinium (225Ac) rhPSMA-10.1 in people with Metastatic Castration-resistant Prostate Cancer and Metastatic Prostate Cancer, run by University College, London at 1 site in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Advanced metastatic castration-resistant prostate cancer is a medical condition for which additional effective and tolerable treatments are urgently needed in order to improve patient outcomes and quality of life. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Actinium (225Ac) rhPSMA-10.1
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited Kingdom
Study dates
13 Apr 2026to 30 Dec 2031
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Age ≥ 18 years at time of providing informed consent.
  • Histologically- or cytologically-confirmed diagnosis of prostate adenocarcinoma, which may include small cell or neuroendocrine features.
  • Castration-resistant prostate cancer, defined as a rising PSA despite surgical castration or ongoing medical castration, with serum testosterone ≤ 0.5ng/mL or <1.7 nmol/L.
  • Progressive mCRPC with rising PSA level, as defined by PCWG3 criteria, or by radiological progression, and must demonstrate a sequence of rising values above baseline at a minimum of 1-week intervals and PSA > 1 ng/mL.
  • PSMA-avid disease on screening PSMA-PET-CT scan
  • Prior treatment with at least one second-generation androgen receptor pathway inhibitor (ARPI)
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  • Prior treatment with at least one but no more than two lines of taxane therapy for prostate cancer, or been deemed ineligible or refused taxane therapy on consultation with their treating physician.
  • At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of trial treatment. Anti-cancer treatment includes ARPIs and PARP inhibitors but excludes ADT (e.g. luteinising hormone releasing hormone (LHRH) analogue or gonadotropin-releasing hormone treatment), which should be continued. Prednisone up to 10 mg daily (or equivalent) is also permitted.
  • Prior treatment with 177Lu-PSMA-targeted radiopharmaceutical therapy (e.g. 177Lu-PSMA-617, 177Lu PSMA-I\&T) up to a maximum of 6 cycles and with response to therapy as judged by the treating physician.
  • Exception: in Phase I, the first 3 participants treated at each dose level may be 177Lu-PSMA naïve Note: last treatment with 177Lu-PSMA must be more than 10 weeks prior to study enrolment.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
  • Estimated life expectancy > 12 weeks.
  • Grade ≤ 1 xerostomia symptoms at time of trial enrolment.
  • Adequate bone marrow, renal, and hepatic function
  • Resolution of all previous treatment-related toxicities to CTCAE v5.0 Grade ≤ 1, except for chemotherapy-induced alopecia, Grade 2 peripheral neuropathy, and Grade 2 urinary frequency, which are permitted.
  • Adequate contraception for participants and their partners.
  • Willing and able to provide written informed consent.

Who cannot join

  • Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
  • Active metastatic central nervous system (CNS) disease, including leptomeningeal disease.
  • Receipt of 177Lu-PSMA treatment within 10 weeks of trial enrolment.
  • Prior radiotherapeutic treatment for metastatic prostate cancer (e.g. Radium-223) with the exception of 177Lu-PSMA.
  • Note: prior radiotherapeutic treatment for other cancers is permitted (e.g. radioactive iodine for thyroid cancer).
  • Receipt of transfused blood products or erythropoietin stimulating agents within 4 weeks of trial enrolment.
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  • Major surgery within 12 weeks of trial enrolment.
  • Other current malignancy, or malignancy diagnosed/relapsed within the past 5 years (other than non melanomatous skin cancer, stage 0 melanoma in situ, or non-muscle invasive bladder cancer that has undergone curative intent therapy).
  • Sjogren's disease or any other medical conditions that in the judgement of the investigator puts the participant at increased risk of xerostomia.
  • Single kidney, renal transplant or any nephrotoxic condition or concomitant therapy that in the judgement of the investigator could put the participant at risk of unacceptable renal toxicity during the trial.
  • Severe urinary incontinence or any other conditions that in the judgement of the investigator would preclude safe disposal of radioactive urine.
  • Any structural kidney/renal tract disease that in the judgement of the investigator could affect excretion of the trial agent (e.g. hydronephrosis), unless addressed with intervention (e.g. ureteric stent insertion with normalisation of renal function).
  • Clinically significant abnormalities on a single 12-lead electrocardiogram (ECG) during screening evaluation.
  • Concurrent serious conditions that in the judgement of the investigator would pose a safety risk or impair trial participation.
  • Radiation therapy within 2 weeks before trial enrolment.
  • Hypersensitivity to the investigational product or any of its constituents.
  • Current participation in another trial with ongoing receipt of an investigational agent.
  • Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the trial protocol and follow-up schedule, or that would pose a risk to the participant's safety.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Trial Manager contact

02076799274

ncita.actinium@ucl.ac.uk

United Kingdom1 site, 1 recruiting

  • University College London Hospital

    London, WC1E 6BT

    Trial Manager, ncita.actinium@ucl.ac.uk

    Recruiting

Other trials in United Kingdom

About this study

Official title: A Multi-site, Prospective, Open-label Phase I/II Trial of Actinium (225Ac) rhPSMA 10.1 to Evaluate Safety and Anti-tumour Activity in Men With Metastatic Castrate-resistant Prostate Cancer (mCRPC) Including Those Who Have Previously Responded to Lutetium-PSMA

Advanced metastatic castration-resistant prostate cancer is a medical condition for which additional effective and tolerable treatments are urgently needed in order to improve patient outcomes and quality of life.

The goal of this clinical trial is to learn more about Actinium (225Ac) radiohybrid prostate-specific membrane antigen-10.1 (rhPSMA-10.1) injection in men with prostate cancer that has spread and progressed after previous treatments, particularly after Lutetium-PSMA.

Read more

Actinium (225Ac) rhPSMA-10.1 is an injectable radioactive medication that aims to attach to prostate cancer cells in the body and destroy them using ionising radiation. It is a new medication that has not yet been studied in humans.

Participants will receive a dose of Actinium (225Ac) rhPSMA-10.1 every 6 weeks, to a maximum of 6 doses. They will be reviewed regularly by the trial researchers to monitor side effects and safety signals. A range of medication doses will be administered so that researchers can find out what doses of the medication are safe for men with prostate cancer. The trial will also aim to determine how effective this medication is for treating advanced prostate cancer.

Read the detailed description

This is a multi-site, prospective, open-label Phase I/II trial of Actinium (225Ac) rhPSMA-10.1 for men with metastatic castration-resistant prostate cancer (mCRPC). The novel ligand radiohybrid (rh) PSMA-10.1 has shown favourable properties in early clinical and preclinical studies. As an emitter of alpha-radiation, Actinium-225 is expected to deposit greater energy at a shorter range than beta-emitting Lutetium-177, conferring the potential to overcome prior PSMA-based radioligand therapy failure.

Phase I of this trial will focus on dose-finding and medication safety. It will investigate men with mCRPC who have previously responded to Lutetium-PSMA, however, a small number of participants will be permitted to be Lutetium-PSMA-naïve. Participants will additionally be assessed for early signals of treatment activity and there will also be an exploratory dosimetry component.

Phase II will utilise the dose selected from Phase I and expand the treatment cohort. In Phase II all participants are required to have previously responded to Lutetium-PSMA.

Study participants must all undergo a screening process and meet trial criteria before they begin any treatment. Provided they tolerate treatment well and their prostate cancer does not worsen during treatment, participants will be offered further treatment every six weeks, to a maximum of six doses.

Study participants will be reviewed weekly by a trial doctor to ensure they are tolerating treatment well and that any potential side effects of the treatment are identified and addressed. These reviews will sometimes be done remotely e.g. on the phone. Monitoring blood tests will be done regularly, and in Phase II this will also include collection of blood samples for exploratory genetic analysis. After starting treatment, participants will have a CT and bone scan every 12 weeks in order to assess whether their prostate cancer sites are responding to treatment.

After trial treatment is complete, participants will be asked to remain on follow-up to help build an understanding of any long-term impacts of the treatment.

Being tested
Actinium (225Ac) rhPSMA-10.1
Keywords
PSMA, mCRPC, Prostate Cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Actinium (225Ac) rhPSMA-10.1Drug

    Dose will vary depending on trial phase and dose escalation/de-escalation stage

Study groups in NCT07414940
Study groupRoleWhat they receive
Phase I dose escalation/de-escalation of Actinium (225Ac) rhPSMA-10.1ExperimentalParticipants with advanced metastatic castration-resistant prostate cancer (mCRPC) will receive Actinium (225Ac) rhPSMA-10.1. The dose received by successive participants will be determined according to a pre-specified dose escalation/de-escalation scheme.
Receives: Drug: Actinium (225Ac) rhPSMA-10.1
Phase II cohort expansion at recommended Phase II doseExperimentalParticipants with advanced metastatic castration-resistant prostate cancer (mCRPC) will receive Actinium (225Ac) rhPSMA-10.1 at the recommended Phase II dose determined in Phase I.
Receives: Drug: Actinium (225Ac) rhPSMA-10.1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I incidence of dose-limiting toxicities (DLTs)

    Incidence of DLTs during the DLT observation period

    Measured: From time of IMP administration until completion of the dose-limiting toxicity period, which is 6 weeks.

  2. Phase II anti-tumour response

    Proportion of patients with response to treatment, defined as either (or both) of: PSA reduction of ≥ 50% from baseline (PSA50), objective radiographic response as assessed by imaging using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) with Prostate Cancer Working Group 3 (PCWG3) recommendations

    Measured: From date of IMP administration until the occurrence of PSA nadir (for PSA50) or best radiographic response (for Objective Radiographic Response), monitored for a maximum of 5 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2026
  2. Study start13 Apr 2026
  3. Primary completion30 Mar 2031 (estimated)
  4. Study completion30 Dec 2031 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase I: dose escalation/de-escalation, Phase II: cohort expansion at recommended Phase II dose
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07414940
Sponsor's protocol ID
158145
Acronym
ACT-RESoLUTE
Status last verified
Apr 2026
First submitted
22 Aug 2024
Last updated
8 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Actinium (225Ac) rhPSMA-10.1 in people with Metastatic Castration-resistant Prostate Cancer and Metastatic Prostate Cancer, run by University College, London at 1 site in United Kingdom.

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 17 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 8 May 2026. 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 United Kingdom. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Trial Manager (02076799274, ncita.actinium@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I incidence of dose-limiting toxicities (DLTs) (time frame: From time of IMP administration until completion of the dose-limiting toxicity period, which is 6 weeks.). The study lists 2 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 NCT07414940.

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 8 May 2026.

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