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

NCT07038304 | Recruiting Phase 2 DMC

• 1 other identifier: NL87430.042.24
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• NEST-FS

  Next line systemic treatment free survival

  6, 12-and 24-months

• rPFS

  radiologic progression free survival

  6, 12-and 24-months

Secondary Outcomes (12)

• Quality of Life (QoL)

  baseline, 6 months, 12 months, 24 months

• Biochemical progression

  From date of randomization until the date of first documented biochmical progression, assessed up to 36 months

• Overall survival (OS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

• Quality of life (QoL)

  baseline, 6 months, 12 months, 24 months

• Acute grade ≥ 2 gastrointestinal toxicity

  Up to 3 months after completion of the RT

Study Arms (1)

MDRT to oligoprogression

EXPERIMENTAL

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

Radiation: Metastasis directed radiotherapy

Interventions

Metastasis directed radiotherapy 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.

MDRT to oligoprogression

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Prostate cancer is limited to males.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (2)

UMC Groningen

Groningen, Netherlands

RECRUITING

Radboud Umc

Nijmegen, Netherlands

NOT YET RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Central Study Contacts

Shafak Aluwini

CONTACT

+31625649975; s.al-uwini@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: June 26, 2025
• Study Start: January 3, 2025
• Primary Completion (Estimated): January 3, 2028
• Study Completion (Estimated): January 3, 2029
• Last Updated: June 26, 2025

Record last verified: 2025-06

Locations

NL (2)