The Radium-select Study

68Ga-PSMA-PET/CT and Genomic Alterations for Future Selection of Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) for Radium-223 Treatment.

Radium-223 is an established radionuclide therapy for patients with metastatic castration resistant prostate cancer (mCRPC) and symptomatic bone metastasis. Patients are eligible for this treatment when they have mCRPC and bone metastases; limited extraskeletal lesions (local prostate, lymph nodes <3 cm) on conventional contrast enhanced CT (ceCT) were allowed in the registration trial(1). Previous research revealed that extraskeletal disease on ceCT and bone scans correlates with a poor response. Meanwhile, 68Ga-PSMA-PET/CT emerged as more sensitive imaging strategy that increases the detection of extraskeletal prostate cancer metastases. It is unclear whether these extraskeletal lesions harbour any predictive value in the treatment of mCRPC patients with Radium-223.

Study Overview

• Status: Recruiting
• Conditions: Male Urogenital Diseases; mCRPC
• Intervention / Treatment: Other: 68Ga-PSMA-PET/CT scan

Detailed Description

Study design:

The investigators will conduct a prospective clinical study in which patients with mCRPC and bone-only disease according to ceCT and bone scan will receive standard-of-care treatment with Radium-223. In addition to standard-of-care systemic treatment, each patient will undergo an additional 68Ga-PSMA-PET/CT scan at baseline and will be followed throughout the treatment with patient reported outcome measure (PROM) questionnaires (Kaiku application) and blood sampling for circulating tumor DNA (ctDNA) analysis. The treating physicians will be blinded to the result of the baseline 68Ga-PSMA-PET/CT scan. Each patient will receive a maximum number of 6 cycles of Radium-223 therapy according to current clinical guidelines and will undergo response evaluation by ceCT and bone scans upon clinical progression. At clinical progression, each patient will undergo a second 68Ga-PSMA-PET/CT to determine the location of disease progression and assess the value of 68Ga-PSMA-PET/CT imaging as a response measure. The clinical response of Radium-223 therapy in the patients with bone-only disease according to 68Ga-PSMA-PET/CT scanning, will be compared to the treatment outcomes collected in our previously reported ROTOR registry. Secondary aims are to determine the value of ctDNA as predictive biomarker and the value of 68Ga-PSMA-PET/CT imaging in the response assessment.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: J.C. van der Mijn, Dr.; Phone Number: +31205129111; Email: k.vd.mijn@nki.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3582KE
    • Not yet recruiting
    • Diakonessenhuis
    • Contact: Tanja Oostergo, MD, MSc; Phone Number: +31 88 250 9810; Email: toostergo@diakhuis.nl
  • Utrecht, Netherlands, 3584CX
    • Recruiting
    • UMC
    • Contact: Marnix Lam, MD, PhD; Phone Number: +31887555555; Email: m.lam@umcutrecht.nl
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066CX
      • Recruiting
      • NKI-AvL
      • Contact: J.C. van der Mijn, MD, PhD; Phone Number: +31205129111; Email: k.vd.mijn@nki.nl
      • Principal Investigator: Koen van der Mijn, MD, PhD
  • Utrecht
    • Amersfoort, Utrecht, Netherlands, 3813TZ
      • Recruiting
      • Meander Medisch Centrum
      • Contact: Joyce Dodewaard, MD, PhD; Phone Number: +31 (0)33-8501189; Email: jm.van.dodewaard@meandermc.nl
    • Nieuwegein, Utrecht, Netherlands, 3430EM
      • Recruiting
      • Sint Antonius Ziekenhuis
      • Contact: Jules Lavalaye, MD, PhD; Phone Number: +31 883207500; Email: j.lavalaye@antoniusziekenhuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate.
• Progressive disease after previous treatment defined as a rise in serum (Prostate Specific Antigen) PSA (PCWG3 criteria(22), see appendix 1) and/or progression on conventional imaging (PCWG3).
• A positive bone scan (osteoblastic bone metastases), with at least two metastases.
• Hemoglobin concentration >10 g/dl (6.2 mmol/l) and thrombocytes >100 109/I at baseline.
• Each patient will need to (continue to) receive adequate bone protective agents (e.g. bisphosphonates) and androgen deprivation therapy (ADT) according to current clinical guidelines.

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance score >2
• Life expectancy < 6 months.
• Detected extra-skeletal metastases or lymph node metastases (>3 cm short axis) as identified by conventional imaging (ceCT thorax/abdomen)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: mCRPC patients with bone-only disease according to 68Ga-PSMA-PET/CT; a prospective clinical study in which patients with mCRPC and bone-only disease according to ceCT and bone scan will receive standard-of-care treatment with Radium-223. In addition to standard-of-care systemic treatment, each patient will undergo an additional 68Ga-PSMA-PET/CT scan at baseline and will be followed throughout the treatment with online patient reported outcome measure (PROM) questionnaires (Kaiku application) and blood sampling for circulating tumor DNA (ctDNA) analysis.

Other: 68Ga-PSMA-PET/CT scan; 68Ga-PSMA-PET/CT scan at baseline and will be followed throughout the treatment with online patient reported outcome measure (PROM) questionnaires (Kaiku application) and blood sampling for circulating tumor DNA (ctDNA) analysis. At clinical progression, each patient will undergo a second 68Ga-PSMA-PET/CT to determine the location of disease progression and assess the value of 68Ga-PSMA-PET/CT imaging as a response measure; Other Names: Blood sampling; Online patient reported outcome measure (PROM) questionnaires

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical progression free survival (cPFS)	The primary study endpoint will be clinical progression free survival (cPFS) in 30 patients with bone-only disease according to PSMA PET/CT.	Up to 28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported outcome measures ( PROMs).	complete questionnaires on health related quality of life (HRQoL), including the (Functional Assessment of Cancer Therapy) FACT-P: Score 1 to 4, Brief pain Inventory (BPI-SF): scale score from 1 to 10, and analgesics use; name, dosing, frequence and after every treatment cycle.	In screening and cycle 2,3,4,5,6 (every 4 weeks) and with progression
Overall survival (OS)	OS will be defined as time from first Radium-223 treatment to the date of death, or censored at last follow-up.	In Follow up (q6months, max 24 months)
Baseline and changes in 68 Ga-PSMA-PET-CT parameters	Baseline and changes in 68Ga-PSMA-PET/CT parameters (disease localizations, extent of disease, tumor volume).	Baseline and until progression
Genomic biomarkers in ctDNA	We will determine whether homologous recombination deficiency (HRD) assessment in ctDNA correlates with a favorable therapy response. We will perform deep whole genome sequencing (WGS) of ctDNA to determine the clonal evolution of prostate cancer during Radium-223 therapy.	Before treatment, cycle 3 and 5 and with progression

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Bayer
• Investigators: Principal Investigator: J.C. van der Mijn, NKI-AvL

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: August 16, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 4, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Radium-223; mCRPC; 68Ga-PSMA-PET/CT; Bone only-disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Gallium 68 PSMA-11
• Other Study ID Numbers: M24PSM; NL86928.041.24 (Registry Identifier: ABR formulier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No