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RecruitingLast updated: 7 July 2026

AcTFirst: Comparing a targeted radioactive treatment with standard treatments for people with advanced prostate cancer (mCRPC)A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer

Trial purpose

Medical clipboardCancer treatment

Tumor type

Urinary System Cancers Genitourinary

Age

People18 - 100

Trial acronym

AcTFirst

Clinical summary

Summary

This study is looking at whether a new type of targeted radioactive treatment called [225Ac]Ac-PSMA-617 works better than standard treatments for advanced prostate cancer.

The main goal is to see if the new treatment can slow down the growth or spread of cancer for longer.

[225Ac]Ac-PSMA-617 (also known as AAA817) is a targeted radioligand therapy. It is designed to attach itself to PSMA, a protein found on prostate cancer cells, and deliver radiation directly to those cells.

It may be given with hormone therapy, whichworks by lowering or blocking the hormones that help prostate cancer grow.

Who is this study for?
You may be able to take part if:

  • you have prostate cancer that has spread (metastatic)
  • your cancer no longer responds to hormone therapy (castration-resistant)
  • your cancer shows PSMA
  • you have already had one type of hormone therapy (ARPI)

You may not be able to take part if you have had:

  • chemotherapy for advanced prostate cancer, or
  • previous PSMA-targeted radioactive treatment

What does taking part involve?
First, there will be a screening period where participants will have tests to check if the study is suitable for them. This includes a PET/CT scan to confirm their cancer is PSMA-positive.

Participants will be randomly assigned (by chance) to one of two treatment groups.

  • Investigational group: 
    • Up to 6 doses of [225Ac]Ac-PSMA-617
    • Given through a drip into the vein (IV)
    • May also take hormone therapy tablets (enzalutamide or abiraterone)
  • Standard treatment group - Doctor will choose one of the following treatments:
    • Hormone therapy tablets (enzalutamide or abiraterone)
    • Chemotherapy (docetaxel or cabazitaxel)
    • Another PSMA-targeted treatment ([177Lu]Lu-PSMA-617)

During the study, participants will have regular check-ups to monitor their health and any side effects. They can receive supportive care (such as treatments to manage symptoms), including ongoing hormone therapy. Participants cannot switch between treatment groups once assigned.

Conditions

This trial is treating people with metastatic castration-resistant prostate cancer that is PSMA positive

Eligibility

Inclusion

  • Signed informed consent must be obtained prior to participation in the study.
  • Participants must be adults ≥ 18 years of age.
  • Participants must have an ECOG performance status of 0 to 2.
  • Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
  • Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
  • Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
  • Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
  • Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting as their last treatment (and did not progress on more than one ARPI).

    • Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.

Exclusion

  • Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, [177Lu]Lu-PSMA, [177Lu]-DOTA, or Radium- 223.)
  • Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).

    • Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC). Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization.

Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.

Other protocol-defined inclusion/exclusion criteria may apply.

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

Trial sponsor

Novartis Pharmaceuticals

Scientific Title

A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer

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