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Metastatic Castration-resistant Prostate CancerPhase 1/2AlphaBetNCT05383079

Combination of Radium-223 and Lutetium-177 PSMA-I&T in Men with Metastatic Castration-Resistant Prostate Cancer

A Phase 1/2 study testing Lutetium-177 PSMA-I&T and Radium-223 in people with Metastatic Castration-resistant Prostate Cancer and MCRPC, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This clinical trial will evaluate the safety of Radium-223 in combination with 177Lu-PSMA-I\&T in metastatic castration-resistant prostate cancer: Phase I/II study Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Lutetium-177 PSMA-I&T and Radium-223
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteAustralia
Study dates
13 Sep 2022to 1 Dec 2026
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

  • Patient must be ≥ 18 years of age and must have provided written informed consent.
  • Histologically or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of metastatic prostate cancer. (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum PSA.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Patients must have progressed on ≥ 1 second-generation AR-targeted agent (e.g., enzalutamide, abiraterone, apalutamide, or darolutamide).
  • Patients must have progressive disease for study entry. PCWG3 defines this as any one of the following:
  • PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement.
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  • Soft tissue progression as per RECIST 1.1 criteria
  • Bone progression: ≥ 2 new lesions on bone scan
  • Symptomatic progression eg. Bone pain
  • At least three weeks since receiving anti-cancer treatment (other than ADT), the completion of surgery or radiotherapy prior to registration.
  • Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
  • Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL) within 28 days before registration.
  • Significant PSMA avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax >10 at sites of measurable disease >10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact).
  • ≥ 2 bone metastases must be present on bone scintigraphy which have not been previously treated with radiotherapy.
  • No contraindication to treatment with a bone antiresorptive agent such as denosumab or zoledronic acid.
  • Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
  • Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last four weeks)
  • Absolute neutrophil count ≥ 1.5x10^9/L
  • Platelets ≥ 150 x10^9/L
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component.
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
  • Albumin ≥ 25 g/L
  • Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft Gault equation
  • Sexually active patients are willing to use medically acceptable forms of barrier contraception.
  • Willing to undergo biopsies, if disease is considered accessible and biopsy is feasible.
  • Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.

Who cannot join

  • Patients who meet any of the following criteria will be excluded from study entry:
  • Superscan on Bone scan (WBBS) or diffuse marrow involvement on PSMA PET/CT
  • Prior treatment with 223Ra or 177Lu-PSMA.
  • Has received more than one previous line of chemotherapy for the treatment of metastatic prostate cancer.
  • Sites of discordant FDG-positive disease defined by minimal PSMA-expression and no uptake on WBBS (for bone metastases).
  • Other malignancies within the previous 2 years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
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  • Symptomatic brain metastases or leptomeningeal metastases.
  • Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.
  • Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

Other trials in Australia

About this study

This clinical trial will evaluate the safety of Radium-223 in combination with 177Lu-PSMA-I\&T in metastatic castration-resistant prostate cancer: Phase I/II study

Read the detailed description

This prospective, single-centre, single-arm, open label, phase I/II trial will assess and establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) of Radium-223 in combination with 177Lu-PSMA-I\&T in patients with mCRPC.

36 men with mCRPC who have progressed on second-generation AR antagonist will be enrolled in this trial in two stages: dose escalation and a dose expansion phase over a period of 24 months.

Being tested
Lutetium-177 PSMA-I&T, Radium-223
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • Lutetium-177 PSMA-I&TDrug

    Patients will be given 7.4 GBq of 177Lu-PSMA every 6 weeks for up to 6 Cycles

  • Radium-223Drug

    During dose escalation, doses of Radium-223 that will be administered include 27.5 kBq/kg and 55 kBq/kg. The maximum tolerated dose of Radium-223 will be used during dose expansion. Radium-223 will be given once every 6 weeks for up to 6 doses between day 1-5 of each Cycle.

Study groups in NCT05383079
Study groupRoleWhat they receive
Radium-223 and Lutetium-177 PSMA-I&TExperimentalIn this single-arm study, patients will receive 7.4 GBq of 177Lu-PSMA-I\&T on Day 1 of every 6 week Cycle. Radium-223 will be administered concurrently every 6 weeks. The dose of Radium-223 will vary in dose-escalation. Up to 6 Cycles will be given.
Receives: Drug: Lutetium-177 PSMA-I&T; Drug: Radium-223

What is being measured

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

  1. Dose Limiting toxicities (DLTs)

    A DLT is defined as a toxicity that prevents further administration of the trial treatment at that dose level.

    Each cohort of 3 patients be assessed for DLTs in the first 6 weeks (cycle 1) of treatment and a dose for the next cohort will be determined.

    Measured: Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.

  2. Maximum Tolerated dose (MTD)

    The MTD is defined as the highest dose level at which the incidence of DLT was less than 2/6.

    Measured: Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.

  3. Recommended Phase 2 Dose (RP2D)

    After the MTD is established, additional patients will be treated at the MTD. Safety and efficacy data from the study will be used to define the RP2D.

    Measured: Up to 30 months from the time the first patient is recruited.

  4. 50% Prostate-Specific Antigen Response Rate (PSA-RR)

    PSA will be assessed at baseline and every 3 weeks from cycle 1 day 1. PSA response will be defined as a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result. A second consecutive value obtained 3 or more weeks later is required to confirm the PSA response.

    Measured: Through study completion, up until 12 months after the last patient commences treatment

Secondary outcomes (8)

  1. Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Safety of the combination will be measured by AEs and SAEs.

    Measured: Through study completion, up until 12 months after the last patient commences treatment

  2. Radiographic Progression-Free Survival (rPFS)

    rPFS is defined as the time from treatment initiation to the first date of documented radiographic progression using conventional imaging or death due to any cause, whichever occurs first. The radiographic progression will be assessed by the investigator per RECIST1.1 for soft tissue and PCWG3 for bone lesions.

    Measured: Through study completion, up until 12 months after the last patient commences treatment

  3. PSA progression free survival (PSA-PFS)

    PSA-PFS is defined as the time from treatment initiation to the date of PSA progression per PCWG3 or death due to any cause, whichever occurs first. The date of PSA progression is the date that an increase of 25% or more and an absolute increase of 2ng/mL or more from the nadir is documented. For patients who have an initial PSA decline during treatment, this must be confirmed by a second value 3 or more weeks later.

    Measured: Through study completion, up until 12 months after the last patient commences treatment

  4. Overall survival (OS)

    OS is defined as the time from treatment initiation to the date of death due to any cause.

    Measured: Through study completion, up until 12 months after the last patient commences treatment

  5. Objective response rate (ORR) by RECIST1.1 in patients with measurable disease

    Objective Response (OR) is only applicable for the subset of patients with measurable disease by RECIST1.1. OR is defined as a partial response (PR) or complete response (CR) at any stage from time of commencement of protocol treatment to the time of subsequent systemic anti-cancer treatment. The ORR is calculated as the proportion of patients with a best response of CR or PR.

    Measured: Through study completion, up until 12 months after the last patient commences treatment

  6. Progression Free Survival (PFS)

    Time from randomisation to the date of PSA progression, or radiographic progression (PCWG3 for bone and RECIST 1.1 for soft tissue), or death.

    Measured: Through study completion, up until 12 months after the last patient commences treatment

  7. Describe pain within 12 months of treatment commencement

    Pain will be assessed using the Brief Pain Inventory - Short Form (BPI-SF). The primary endpoint for pain is the area under the curve (AUC) of the worst pain in 24h.

    Pain and QoL will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months and will be scored according to the respective manuals.

    Measured: Through completion of 12 months after treatment commencement of last patient

  8. Describe health-related QoL within 12 months of treatment commencement

    QoL will be assessed using the Functional Assessment of Cancer Therapy for Prostate Cancer (FACT-P) questionnaire. The primary endpoint for QoL is the area under the curve (AUC) of the trial outcome index (TOI).

    QoL will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months and will be scored according to the respective manuals.

    Measured: Through completion of 12 months after treatment commencement of last patient

Timeline

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

  1. First posted19 May 2022
  2. Study start13 Sep 2022
  3. Primary completion1 Aug 2026 (estimated)
  4. Study completion1 Dec 2026 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05383079
Sponsor's protocol ID
21/029
Acronym
AlphaBet
Status last verified
Nov 2024
First submitted
16 May 2022
Last updated
7 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kostos L, Buteau JP, Xie J, Cardin A, Akhurst T, Alipour R, Au L, Chan J, Chin KY, Emmerson B, Furic L, Garcia Q, Hamilton AJ, Haskali MB, Jackson PA, Kashyap RK, Kong G, MacFarlane L, Murphy DG, Parker BS, Ravi Kumar AS, Saghebi J, Wang Y, Tran B, Azad AA, Hofman MS. Lutetium-177 [177Lu]Lu-PSMA-I&T plus radium-223 in patients with metastatic castration-resistant prostate cancer (AlphaBet): an interim analysis of the investigator-initiated, single-centre, single-arm, phase 1/2 trial. Lancet Oncol. 2025 Nov;26(11):1479-1488. doi: 10.1016/S1470-2045(25)00559-5. Epub 2025 Oct 18.

    PubMed 41119954

  • Kostos L, Buteau JP, Yeung T, Iulio JD, Xie J, Cardin A, Chin KY, Emmerson B, Owen KL, Parker BS, Fettke H, Furic L, Azad AA, Hofman MS. AlphaBet: Combination of Radium-223 and [17 7Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol). Front Med (Lausanne). 2022 Nov 18;9:1059122. doi: 10.3389/fmed.2022.1059122. eCollection 2022.

    PubMed 36465905

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lutetium-177 PSMA-I&T and Radium-223 in people with Metastatic Castration-resistant Prostate Cancer and MCRPC, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

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 26 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 7 Feb 2025. 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 Australia. 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting toxicities (DLTs) (time frame: Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.). The study lists 4 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 NCT05383079, which also lists 2 linked publications.

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 7 Feb 2025.

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