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

NCT ID: NCT05383079

Last Updated: 2025-02-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-13
• Study Completion Date: 2026-12-01

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

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.

Conditions

Metastatic Castration-resistant Prostate Cancer; MCRPC; Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Lutetium-177 PSMA-I&T

Intervention Type: DRUG

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

Radium-223

Intervention Type: 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.

Interventions

Lutetium-177 PSMA-I&T

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

Intervention Type: DRUG

Radium-223

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Prof Michael Hofman

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Locations

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Countries

Australia

References

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 Oct 18:S1470-2045(25)00559-5. doi: 10.1016/S1470-2045(25)00559-5. Online ahead of print.

Reference Type: DERIVED

PMID: 41119954 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36465905 (View on PubMed)

Other Identifiers

21/029

Identifier Type: -

Identifier Source: org_study_id