Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions

NCT06638541 | Recruiting

• 2 other identifiers: CCR5984338368
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 3

Brief Summary

DESTINATION 2 is a multi-centre randomised trial treating intermediate risk localised prostate cancer with 2 fraction Stereotactic Body Radiotherapy (SBRT). All radiotherapy will be delivered in two fractions (sessions) on an MR Linac using daily adaptation. Men will either receive uniform dose radiotherapy or de-escalated dose radiotherapy. The primary endpoint is acute GU CTCAE v5 grade 2+ toxicity. It will also look at late toxicity, patient-reported outcome measures and PSA control.

Conditions

Prostate Cancer

Keywords

De-escalation; Radiotherapy; MR-Linac

Outcome Measures

Primary Outcomes (1)

• Acute GU toxicity

  To describe the absolute risk and relative risk reduction of acute genitourinary (GU) toxicity (CTCAE v5) when delivering de-escalated two fraction prostate SBRT compared to uniform dose two fraction prostate stereotactic body radiotherapy (SBRT) for intermediate risk prostate cancer.

  12 weeks

Secondary Outcomes (8)

• Acute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) toxicity

  Baseline, last fraction, week 2, 4 and 12

• Late Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) toxicity

  Month 6, 12, 24

• Feasibility of radiation delivery

  At time of treatment

• Dosimetry

  At time of treatment

• Patient reported outcome measures

  Baseline, last fraction of treatment, week 2, 4 and 12, 6 months, 1 and 2 years post treatment.

Study Arms (2)

Uniform dose

ACTIVE COMPARATOR

Arm 1 (Uniform dose) will receive 27 Gy in 2 fractions to the whole prostate + seminal vesicles (SV), the CTV, with 0 mm CTV-PTV margin.

Radiation: Prostate radical radiotherapy

De-escalated dose

EXPERIMENTAL

Arm 2 (De-escalated dose) will use two dose levels: The benign prostate (on MRI) will receive 20 Gy in 2 fractions with a 0mm PTV margin. The intraprostatic tumour mass(es) as seen on MRI will receive 27 Gy in 2 fractions. A 4mm GTV-PTV margin will be added to the MR visible tumour to form PTV 27Gy.

Radiation: Prostate radical radiotherapy

Interventions

Prostate radical radiotherapy RADIATION

Radiation: De-escalated radiotherapy to be delivered on the Elekta Unity MR-linac

De-escalated dose; Uniform dose

Eligibility Criteria

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

You may qualify if:

• Men aged ≥18 years
• Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy
• Gleason score 3+3, 3+4 or 4+3 (Grade groups (GG) 1, 2 or 3)
• MRI stage T3a or less (as staged by AJCC TNM 2018). MRI must be performed within a year of randomisation
• MRI-visible tumour(s) of PIRADS v2 grade 3 or higher and able to be delineated on T2 and diffusion-weighted imaging +/- dynamic contrast-enhanced imaging. Tumour nodule visible on MRI should be considered able to be boosted by treating clinician and \<2.5cm in maximal dimension
• Patients can be concurrently treated with androgen deprivation therapy (ADT) if this would be standard of care. LHRH analogues, LHRH agonists or Bicalutamide are permitted. ADT is not mandatory where this would usually be omitted.
• PSA \<20 ng/ml prior to starting ADT, if used
• WHO Performance status 0-2
• Ability of the participant understand and the willingness to sign a written informed consent form.
• Willing to consent to contraception during and for 1 year after treatment when applicable.
• Ability/willingness to comply with the patient reported outcome questionnaires schedule throughout the study.

You may not qualify if:

• Contraindications to MRI (e.g. pacemaker, potentially mobile metal implant, claustrophobia)
• Severe GU symptoms that would preclude extreme hypofractionation per the discretion of the treating physician.
• IPSS Score \> 19
• High grade disease (GG3) occult to MRI-defined lesion. As a guide, any pathology for which you would consider surveillance (eg GG1, low volume GG2) is allowed outside of the MRI-defined area.
• Prostate volume \>90cc
• Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
• Hip replacement, or other pelvic metalwork which causes significant artefact on diffusion-weighted imaging
• Previous pelvic radiotherapy
• Patients needing \>6 months of ADT due to disease parameters.
• Previous invasive malignancy within the last 2 years where this is likely to shorten lifespan the following will remain eligible: basal or squamous carcinomas of the skin, low risk non-muscle invasive bladder cancer (assuming cystoscopic follow up now negative) or small renal masses on surveillance.
• Participating in another interventional trial for prostate cancer

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Elekta Limited: collaborator
• MRL Consortium: collaborator

Study Sites (3)

Sunnybrook Health Sciences Centre

Toronto, Canada

NOT YET RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

Sutton, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Alison Tree

  Royal Marsden Hospital, Institute of Cancer Research

  STUDY CHAIR

Central Study Contacts

Francesca Mason

CONTACT

+44 20 3186 5157; mrltrials@rmh.nhs.uk

Sian Cooper

CONTACT

sian.cooper@rmh.nhs.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: October 15, 2024
• Study Start: January 20, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 23, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: 5 years

Locations

CA (1); GB (2)