NCT07038304

The Impact of Metastatic Directed Radiotherapy (MDRT) on Oligoprogressive Castration Resistant Prostate Cancer (CRPC)

Oligometastatic Directed Radiotherapy for Patients With Castration Resistant Prostate Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In patients with metastatic prostate cancer (PCa) who receive androgen deprivation therapy (ADT), the sensitivity to castration will eventually disappear due to the selection of castration-refractory clones. This will lead to the stage of metastatic castration-refractory prostate can-cer (mCRPC), which is incurable and results in a median overall survival of 2-3 years. Treatment options for patients with mCRPC include several systemic agents, such as andro-gen receptor-targeted agents (ARTA), chemotherapy (docetaxel, cabazitaxel) and bone-targeting agents (radium- 223). Clinical progression and, to a lesser extent, biochemical pro-gression traditionally imply a switch to the next line systemic treatment (NEST). Within patients with mCRPC, there is a subgroup showing oligo-progression, defined as the progression of up to 3 lesions, including both metastatic and/or local relapse. Oligoprogression reflects a heterogeneous treatment response, which, in turn, reflects the heterogeneity of the clonogenic cells that give rise to mCRPC. Retrospective studies suggest that metastasis-directed radiotherapy (MDRT) to these oligoprogressive lesions delayed the need for NEST. Recently, promising results were published on the use of MDRT in the oligopro-gressive mCRPC (omCRPC) setting, with a NEST-free survival (NEST-FS) of 21 months in well selected patients. Currently, in The Netherlands, patients with omCRPC are frequently referred and treated with MDRT, but a clear treatment protocol and inclusion/selection criteria are missing. Moreover, the exact benefit of MDRT in patients with omCRPC remains unclear, as prospective evi-dence for MDRT in omCRPC is lacking.

Detailed description

The primary aim of this study is to test the hypothesis that the addition of MDRT to standard of care (ADT or ADT + chemotherapy or ARTA) in well-selected PCa patients with oligometastatic progressive disease, defined on PSMA PET, prolongs the radiological progression-free survival (rPFS) and postpones the start of next line systemic therapy (NEST). Patients included in this study already have an indication to start NEST, and any delay introduced by adding MDRT will result in a net benefit for the patients. Primary objectives include: Postponement of the start of next line systemic treatment (NEST), and enhancement of the radiological progression-free survival (rPFS) In this single arm multicenter prospective phase II trial, we aim to include 35 patients with omCRPC (1-3 metastases and/or local recurrence) who will be treated with MDRT to the visible progressive lesions (up to max of 3). Progression is based on PSMA PET.

Conditions

• Prostate Cancer (Adenocarcinoma)
• OligoProgressive Metastatic Disease
• Castration Resistant Metastatic Prostate Cancer
• Radiotherapy

Interventions

Type	Name	Description
RADIATION	Metastasis directed radiotherapy	According to guidelines, in the case of oligoprogression next line systemic treatment is recommended. This study investigates the potential delay of NEST and rPFS by MDRT.

Timeline

• Start date: 2025-01-03
• Primary completion: 2028-01-03
• Completion: 2029-01-03
• First posted: 2025-06-26
• Last updated: 2025-06-26

Locations

2 sites across 1 country: Netherlands