The Radium-select Study

Official title

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

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Clinical progression free survival (cPFS) [Time frame: Up to 28 weeks]

Secondary outcome measures (4)

• Patient reported outcome measures ( PROMs). [Time frame: In screening and cycle 2,3,4,5,6 (every 4 weeks) and with progression]
• Overall survival (OS) [Time frame: In Follow up (q6months, max 24 months)]
• Baseline and changes in 68 Ga-PSMA-PET-CT parameters [Time frame: Baseline and until progression]
• Genomic biomarkers in ctDNA [Time frame: Before treatment, cycle 3 and 5 and with progression]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 5 centers

• NKI-AVL — Amsterdam
• Meander Medisch Centrum — Amersfoort
• Sint Antonius ziekenhuis — Nieuwegein
• Diakonessenhuis — Utrecht
• UMC — Utrecht

Identifiers

NCT: NCT06659926 · M24PSM · NL86928.041.24

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗