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Prostate CancerDESTINATION 2NCT06638541

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

A study testing Prostate radical radiotherapy in people with Prostate Cancer, run by Royal Marsden NHS Foundation Trust at 3 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Prostate radical radiotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
3 sitesin 2 countries
Study dates
20 Jan 2025to 1 Jan 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • The MRI-defined lesion must be confirmed as malignant on biopsies (Gleason grade must be within the limits expressed in inclusion factor 3)
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Francesca Mason contact

+44 20 3186 5157

mrltrials@rmh.nhs.uk

Sian Cooper contact

sian.cooper@rmh.nhs.uk

3 sites in 2 countries

United Kingdom2 sites, 2 recruiting

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

    Roonak Nazari, +44(0)161 446 3422, roonak.nazari@nhs.net

    Recruiting

  • The Royal Marsden NHS Foundation Trust

    Sutton

    Francesca Mason, 02031865157, mrltrials@rmh.nhs.uk

    Recruiting

Other trials in United Kingdom

Canada1 site, 1 recruiting

  • Sunnybrook Health Sciences Centre

    Toronto

    Murtuza Saifuddin, 416-480-5000 ext. 63094, murtuza.saifuddin@sunnybrook.ca

    Andrea Deabreu, (416) 480-6100 ext. 61058, Andrea.Deabreu@sunnybrook.ca

    Not yet recruiting

Other trials in Canada

About this study

Official title: Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions - a Randomised Trial

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.

Read the detailed description

54 patients meeting inclusion criteria will be randomised between two arms. 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. 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. The primary endpoint is emergent acute GU CTCAE v5 Grade 2+ toxicity, recorded within 3 months of completing radiotherapy. Secondary endpoints are CT CAE v5 acute GI toxicity, late toxicity, patient-reported outcome measures (PROMs) (EPIC-26, IPSS, and IIEF-5) at 4 and 12 weeks, 6 months, 1 and 2 years post treatment, PSA control and kinetics

Conditions
Prostate Cancer
Being tested
Prostate radical radiotherapy
Keywords
De-escalation, Radiotherapy, MR-Linac
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Prostate radical radiotherapyRadiation

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

Study groups in NCT06638541
Study groupRoleWhat they receive
Uniform doseActive comparatorArm 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.
Receives: Radiation: Prostate radical radiotherapy
De-escalated doseExperimentalArm 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.
Receives: Radiation: Prostate radical radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 weeks

Secondary outcomes (8)

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

    To describe the absolute and relative risk of toxicity

    Measured: Baseline, last fraction, week 2, 4 and 12

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

    To describe the absolute and relative risk of toxicity

    Measured: Month 6, 12, 24

  3. Feasibility of radiation delivery

    Feasibility- estimate percentage of fractions interrupted due to patient discomfort

    Measured: At time of treatment

  4. Dosimetry

    Dosimetry- estimate the accumulated dose differences between the de-escalated and uniform dose delivery

    Measured: At time of treatment

  5. Patient reported outcome measures

    To assess baseline, acute and late International Prostate Symptom Score (IPSS). IPSS ranges from 0 to 35. Lower scores are better: A lower score indicates fewer or less severe urinary symptoms, while a higher score suggests more severe symptoms.

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

  6. Patient reported outcome measures

    Expanded Prostate Cancer Index Composite Short Form (EPIC-26). EPIC-26 scores are transformed to a 0-100 scale for each domain.The questionnaire usually covers urinary incontinence, urinary irritative/obstructive symptoms, bowel, sexual, and hormonal functions. Higher scores represent better health-related quality of life.

    Measured: Baseline, 4 and 12 weeks, 6 months, 1 and 2 years post treatment.

  7. Patient reported outcome measures

    International Index of Erectile Function-5 (IIEF-5). The IIEF-5 score ranges from 5 to 25. Higher scores are better: A higher score indicates better erectile function, while a lower score suggests more severe erectile dysfunction.

    Measured: Baseline, 6 months, 1 and 2 years post treatment.

  8. PSA kinetics

    To assess biochemical relapse-free survival at 2 years

    Measured: Baseline (pre ADT), week 12, month 6, and 1 and 2 years post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2024
  2. Study start20 Jan 2025
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06638541
Sponsor's protocol ID
CCR5984
Other IDs
338368
Acronym
DESTINATION 2
Status last verified
Jul 2025
First submitted
23 Sep 2024
Last updated
23 Mar 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: It is intended that data will be shared within the MOMENTUM collaboration, between centres delivering treatment in the same way as DESTINATION2. Pseudonymised data will be stored within MOMENTUM for at least 5 years. Storage will be cloud based and as the treating centre we will have free access to the data and control over who else can assess it.

Publications

  • Cooper S, Alexander S, Breitkreutz D, Casey F, Christodouleas J, Dassen MG, Dell'acqua V, Dunlop A, Herbert T, Kolias P, Mitchell A, Pos FJ, Westley R, Tree AC, Van Der Heide UA, Vesprini D. Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions (DESTINATION 2): protocol for a randomised, phase II/R-IDEAL2b trial. BMJ Open. 2026 May 7;16(5):e111791. doi: 10.1136/bmjopen-2025-111791.

    PubMed 42097645

Questions about this trial

What is this clinical trial studying?

A study testing Prostate radical radiotherapy in people with Prostate Cancer, run by Royal Marsden NHS Foundation Trust at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Francesca Mason (+44 20 3186 5157, mrltrials@rmh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Acute GU toxicity (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06638541, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026; AzTrials last refreshed its copy on 30 Oct 2026.

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