Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer

NCT04983095 | Recruiting DMC

• 1 other identifier: METRO_vers1
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 7

Brief Summary

The study is an open label, multi-centre, randomized phase III study. The patients will be randomised in a 1:1 ratio to treatment consisting of

• Arm A: MD-SBRT in addition to standard treatment
• Arm B: Standard treatment Study population: Patients with hormone sensitive prostate cancer (HSPC) with oligometastatic disease detected by PSMA-PET/DT. This includes patients with de novo oligometastatic HSPC and recurrent HSPC after primary RT or prostatectomy. Primary endpoint: Failure free survival Secondary endpoints:
• Predictive value of investigated biomarkers in blood and imaging
• Acute and late toxicity after MD-SBRT
• PROM at 3 months, 1, 3 and 5 years
• Castration resistant prostate cancer, CRPC
• Overall survival
• Differences in outcome between patients by strata Stratification: To avoid imbalance between treatment arms the minimisation method will be used to achieve balance between de novo oligo-metastatic and oligo-recurrent patients, as well as treatment site. Safety evaluation: Adverse events and side effects graded according to CTCAE v5.0 will be collected every 6th month. Serious Adverse Events are to be reported within 24 hours throughout the study duration. Statistical methods: Survival endpoints will be calculated using the Kaplan-Meier method with differences compared using the stratified log-rank test. Randomization time is set as baseline time. Pre-planned subgroup analysis will occur based on pre-specified stratification variables. A Cox multivariable regression model will be used to determine factors predictive of survival. Safety analysis will be performed with Mann-Whitney U-test or Fishers exact test. Criteria for evaluation: Per protocol (patients that have started study treatment) and Intention to treat (all included patients). Planned sample size: 118 patients Analysis plan: The primary end point will be analysed after pre-specified number of events have occurred. All patients randomised to SBRT will be followed minimum 60 months for toxicity. Safety analysis of acute toxicity will take place after median follow up of 6 months. Safety analysis of late toxicity will be analysed after study closure. Duration of the study: Three to five years inclusion. 72 months of follow-up after randomization of the last patient.

Conditions

Prostate Cancer Metastatic; Radiation Therapy; Positron-Emission Tomography

Keywords

Oligometastatic Prostate Cancer; Hormone Sensitive; Stereotactic Body Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Failure free survival

  Time from randomisation to progressive disease. Progression is defined as 2 consecutive rises in blood PSA. PSA will be collected every third month and registered in the electronic case report form.

  Throughout the study duration (72 months of follow up for last patient included.)

Secondary Outcomes (6)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.

  Until 6 months after randomisation

• Number of participants with treatment-related serious adverse events as assessed by CTCAE v5.

  Throughout the study duration (72 months of follow up for last patient included.)

• Outcome prediction

  Throughout the study duration (72 months of follow up for last patient included.)

• Patient reported quality of life assessed by EORTC-QLQ 30

  Throughout the study duration (72 months of follow up for last patient included.)

• Overall survival

  Throughout the study duration (72 months of follow up for last patient included.)

Other Outcomes (1)

• outcome according to strata

  Throughout the study duration (72 months of follow up for last patient included.)

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

ADT+ARPI to all patients and local RT +/- pelvic fields to de novo patients

Combination Product: androgen deprivation therapy; Radiation: Radiotherapy

SBRT+Standard of Care

EXPERIMENTAL

SBRT to all PSMA+ lesions in addition to SoC and salvage RT to the prostate bed +/- pelvic fields if recurrent post prostatectomy and PSMA-PET+ in the pelvis

Radiation: stereotactic body radiotherapy; Combination Product: androgen deprivation therapy; Radiation: Radiotherapy

Interventions

stereotactic body radiotherapy RADIATION

30 Gy in 3 fractions alternatively 40 Gy in 5 fractions delivered with stereotactic radiotherapy-principles

Also known as: stereotactic ablative radiotherapy, image guided radiotherapy

SBRT+Standard of Care

androgen deprivation therapy COMBINATION_PRODUCT

Medical castration and next-generation Hormonal Agent along with radiotherapy to the prostate in de novo oligometastatic prostate cancer

Also known as: gonadotropin releasing hormone-agonist, gonadotropin releasing hormone-antagonist, androgen-receptor pathway inhibitor (ARPI)

SBRT+Standard of Care; Standard of Care

Radiotherapy RADIATION

RT to the prostate for de novo patients

Also known as: external radiotherapy

SBRT+Standard of Care; Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed prostate cancer (ICD-O-3 C61)
• WHO/ECOG performance status 0-1
• skeletal or extra pelvic lymph node metastases detected by PSMA-PET/CT in de novo prostate cancer or PSA-relapse after definitive RT or prostatectomy
• Willing and able to provide informed consent-

You may not qualify if:

• Castration resistant prostate cancer (progression with castrate levels of testosterone)
• Any treatment known to affect PSA (including ADT) for prostate cancer within 6 months (exception: ADT started due to oligometastatic disease within 2 weeks of study entry)
• Patient eligible for other treatment (e.g., early docetaxel) than standard treatment described in the protocol as judged by treating physician
• Life expectancy \<3 years by any reason, including concomitant or previous malignancies
• Previous radiotherapy or surgery that may interfere with the planned treatment (including intra-prostatic recurrence if previous RT to the prostate)
• \> 3 PSMA-PET/CT positive target lesions (excluding the prostate and regional lymph node metastasis in de novo patients or prostate bed and or regional lymph node metastasis in recurrent patients)
• PSMA-PET verified metastases other than skeletal or lymph nodes
• Metastases in base of scull and/or calotte
• Any target lesions not treatable with image guided RT (IGRT) due to overlap with previous RT fields or exceeded dose constraint to OAR(s) as specified in study protocol

Sponsors & Collaborators

• Stockholm South General Hospital: collaborator
• Region Skane: collaborator
• Ryhov County Hospital: collaborator
• Sahlgrenska University Hospital: collaborator
• Trondheim University Hospital: collaborator
• Capio Sankt Görans Hospital: collaborator
• Alesund Hospital: collaborator
• Region Örebro County: collaborator
• Karin Soderkvist: lead
• University Hospital, Umeå: collaborator
• Karolinska University Hospital: collaborator

Study Sites (7)

Region Skåne

Lund, Lund, Sweden

RECRUITING

Capio St Göran Hospital

Stockholm, Region Stockholm, Sweden

RECRUITING

Södersjukhuset

Stockholm, Region Stockholm, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, Stockholm County, Sweden

RECRUITING

Umeå University hospital

Umeå, Umea, 90331, Sweden

RECRUITING

Ryhovs county hospital

Jönköping, Sweden

RECRUITING

Region Örebro Län

Örebro, Örebro County, Sweden

RECRUITING

Related Publications (1)

• Soderkvist K, Zia M, Gunnlaugsson A, Josefsson A, Aksnessaether B, Li C, Thellenberg-Karlsson C, Alm D, Kudren D, Lundin E, Moise G, Brandell JK, Kindblom J, Bjornlinger K, Karlsson K, Riklund K, Westin M, Hedman M, Skorve N, Wikstrom P, Strandberg S, Jonsson J. Metastasis-directed SBRT for oligometastatic hormone sensitive prostate cancer (METRO): protocol for a prospective randomised phase III trial, NCT04983095. BMC Cancer. 2026 Mar 25. doi: 10.1186/s12885-026-15906-6. Online ahead of print.

  PMID: 41882599 DERIVED

Related Links

• Official site for clinical trials by Swedish Regional Cancer Centres in Collaboration

MeSH Terms

Interventions

Radiosurgery; Radiotherapy, Image-Guided; Androgen Antagonists; Gonadotropin-Releasing Hormone; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Karin Söderkvist

  Region Västerbotten, Umeå University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karin Söderkvist, MD,PhD

CONTACT

+46 90 7853222; karin.soderkvist@umu.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Consultant, PhD

Model Details: Patients are randomised to control (standard care)1:1 intervention (SBRT+standard care)

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: July 30, 2021
• Study Start: October 27, 2021
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 1, 2033
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Planned publication of study at study start
• Access Criteria: Open access publication

Locations

SE (7)