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

NCT ID: NCT07038304

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-03
• Study Completion Date: 2029-01-03

Brief 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

Study Design

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

Study Groups

MDRT to oligoprogression

Patients included in the study with a post prostatectomy local recurrence on the PSMA PET with up to 3 oligometastases will be treated preferably with SBRT to all oligometastatic lesions and to the local recurrence in prostate bed

Group Type: EXPERIMENTAL

Metastasis directed radiotherapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Adenocarcinoma of the prostate.
• mCRPC setting, with testosterone level < 50 ng/dl or 1.7 nmol/l.
• Oligoprogressive disease diagnosed on PSMAscan; defined as the progression of pre-existing metastatic disease, and/or the appearance of new metastases and/or the appearance of a local relapse with a maximum of 3 lesions in total.
• Patients currently treated with ADT, whether combined with another systemic treatment such as ARTA, chemotherapy.
• For patients treated with chemotherapy, the course should be completed or stopped before start MORT - In case of treatment with ARTA, a minimal of 3 months response (PSA or clinical response).
• WHO performance status 0-2.
• Age > = 18 years old.
• Patiënt should be presented at the multidisciplinary tumor board of the local hospital in which the therapy will be given.
• Before patiënt registration, written informed consent must be given according to ICH/GCO and national/local regulations.

Exclusion Criteria

• Serum testosterone level > 50 ng/ml or > 1.7 nmol/l.
• Presence of more than 3 progressive/new metastatic lesions and/or local recurrence (which counts for 1 lesion).
• Active malignancy other than prostate cancer that can potentially interfere with the interpretation of the trial, except non-melanoma skin cancer or non-invasive urothelial cell carcinoma.
• Local recurrence in the prostate after previous radiotherapy
• Previous treatments (RT, surgery) or comorbidities making new treatment with MDRT impossible.
• Disorder precluding understanding of trial Information or informed consent or signing informed consent.
• Evidence of PSMA-negative disease.

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

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UMC Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Radboud Umc

Nijmegen, , Netherlands

Site Status: NOT_YET_RECRUITING

Countries

Netherlands

Central Contacts

Shafak Aluwini

Role: CONTACT

s.al-uwini@umcg.nl

+31625649975

Facility Contacts

Shafak Aluwini

Role: primary

s.al-uwini@umcg.nl

+31625649975

Robert Jan Smeenk

Role: primary

RobertJan.Smeenk@radboudumc.nl

+31 (024) 361 45 05

Other Identifiers

NL87430.042.24

Identifier Type: -

Identifier Source: org_study_id