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

NCT05383079 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 21/029
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Metastatic Castration-resistant Prostate Cancer; MCRPC; Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• 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.

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

• Maximum Tolerated dose (MTD)

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

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

• 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.

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

• 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.

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

Secondary Outcomes (8)

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

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

• Radiographic Progression-Free Survival (rPFS)

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

• PSA progression free survival (PSA-PFS)

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

• Overall survival (OS)

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

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

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

Study Arms (1)

Radium-223 and Lutetium-177 PSMA-I&T

EXPERIMENTAL

In 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.

Drug: Lutetium-177 PSMA-I&T; Drug: Radium-223

Interventions

Lutetium-177 PSMA-I&T DRUG

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

Radium-223 and Lutetium-177 PSMA-I&T

Radium-223 DRUG

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.

Radium-223 and Lutetium-177 PSMA-I&T

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Related Publications (2)

• 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.

  PMID: 41119954 DERIVED

• 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.

  PMID: 36465905 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radium-223

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Prof Michael Hofman

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 19, 2022
• Study Start: September 13, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 7, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)