Dose-Escalated MR-Guided Radiotherapy for Localized Prostate Cancer

NCT07674225 | Active Not Recruiting DMC

• 1 other identifier: 6617
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Intermediate Risk Prostate Cancer (Diagnosis); Prostate Cancer

Keywords

DESTINATION 2,; Prostate Cancer; Intermediate Risk Prostate Cancer; 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, at completion of radiotherapy, Week 2, Week 4, and Week 12

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

  Month 6, 12, 24

• Feasibility of radiation delivery

  During each treatment fraction

• Dosimetry

  During each treatment fraction

• Patient reported outcome measures

  Baseline, at completion of radiotherapy, Week 2, Week 4, Week 12, 6 months, 1 year, and 2 years after treatment completion

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

All radiotherapy will be delivered in two fractions (sessions) on an MR Linac using daily adaptation.

Uniform dose

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participants must be biologically male with a diagnosis of prostate cancer
• 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
• Short course (\< 6 months) concurrent androgen deprivation therapy (antiandrogens or LHRH analogues) allowed though not mandated as per the discretion of the treating physician.
• 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.
• 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)
• IPSS Score \> 19
• High grade disease (GG3) occult to MRI-defined lesion.
• 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, as per the discretion of the treating physician
• 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.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Elekta Limited: collaborator
• MRL Consortium: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4Y 2J3, Canada

Location

Related Publications (4)

• Dess RT, Hartman HE, Aghdam N, Jackson WC, Soni PD, Abugharib AE, Suy S, Desai NB, Zumsteg ZS, Mehra R, Morgan TM, Feng FY, Hamstra DA, Schipper MJ, Collins SP, Spratt DE. Erectile function after stereotactic body radiotherapy for localized prostate cancer. BJU Int. 2018 Jan;121(1):61-68. doi: 10.1111/bju.13962. Epub 2017 Aug 17.

  PMID: 28710895 BACKGROUND

• Brand DH, Tree AC, Ostler P, van der Voet H, Loblaw A, Chu W, Ford D, Tolan S, Jain S, Martin A, Staffurth J, Camilleri P, Kancherla K, Frew J, Chan A, Dayes IS, Henderson D, Brown S, Cruickshank C, Burnett S, Duffton A, Griffin C, Hinder V, Morrison K, Naismith O, Hall E, van As N; PACE Trial Investigators. Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol. 2019 Nov;20(11):1531-1543. doi: 10.1016/S1470-2045(19)30569-8. Epub 2019 Sep 17.

  PMID: 31540791 BACKGROUND

• Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O'Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E; CHHiP Investigators. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016 Aug;17(8):1047-1060. doi: 10.1016/S1470-2045(16)30102-4. Epub 2016 Jun 20.

  PMID: 27339115 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

MeSH Terms

Conditions

Disease; Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Dr. Danny Vesprini, MSc, MD, FRCPC

  Sunnybrook Odette Cancer Centre, University of Toronto

  PRINCIPAL INVESTIGATOR

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: May 13, 2026
• First Posted: June 29, 2026
• Study Start: March 22, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: June 29, 2026

Record last verified: 2026-05

Data Sharing

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

Locations

CA (1)