Clinical trial NCT06177093: De-escalated Dose SBRT in Localized Prostate Cancer (DESTINATION-MRL)
Official title: A Pilot Study of Dose dE-eScalaTion IN prostATe radIOtherapy usiNg the MRL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate Cancer
Keywords: Newly diagnosed intermediate risk localized prostate cancer
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2023-12-20
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single centre phase II non-randomized study
Primary purpose: TREATMENT

Brief summary: This study is a single centre feasibility trial. The trial will recruit men with intermediate risk localised prostate cancer who will all receive targeted dose (escalated/de-escalated dose directed by MRI) 5 fraction SBRT to the prostate.

Trial Objectives are:

1. Primary To develop a 5 fraction de-escalated dose SBRT protocol capable of reducing side effects
2. Secondary

   * To assess levels of acute GU and GI toxicity (CTCAE)
   * To assess levels of late GU and GI toxicity (CTCAE)
   * To assess late sexual quality of life (expanded EPIC, IIEF-5)
   * To assess biochemical relapse-free survival at 2

Detailed description: TRIAL POPULATION: Men with intermediate risk localized prostate cancer TRIAL TREATMENT: All radiotherapy will be delivered on the MR-linac. Intraprostatic dose will be varied according to risk of local recurrence, based on mpMRI, PSA and histology. The whole prostate will receive 30 Gy in 5 fractions and the dominant lesion plus intra-prostatic margin will receive an isotoxic 45 Gy prescription.

Study rationale: The DESTINATION project aims to establish whether focusing radiation dose on the area most at risk of recurrence, and reducing the dose elsewhere, can produce a low level of side effects and maximize quality of life. This trial will assess technical feasibility of this approach.

TRIAL DESIGN: DESTINATION is run as a single centre trial embedded within the Sunnybrook REB approved MOMENTUM collaboration. The MOMENTUM trial facilitates data sharing across participating institutes.

Patients will be reviewed and complete toxicity assessments (CTCAE version 5) at the end of their radiation and then at 4 and 12 weeks after completion of treatment. They will thereafter be assessed at 6, 12 and 24 months with CTCAE version 5 and the patient reported IPSS assessment completed at each time point. Thereafter follow up will be as per standard care. Patient reported EPIC-26 will be measured at; baseline, 4 and 12 weeks, and 6, 12 and 24 months from the end of radiotherapy. IIEF-5 will be completed at months 6, 12 and 24. Scans will be taken before and during radiotherapy on the MR-linac. Patients will be followed up for recurrence/biochemical failure on protocol for 24 months and thereafter as per standard of care.

Eligibility criteria: Inclusion Criteria:

* Men aged ≥18 years
* Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy
* Gleason score 3+3, 3+4 or 4+3 (Grade groups 1, 2 or 3)
* MRI stage T2 or less (as staged by AJCC TNM 2018)
* MRI-visible tumour(s) of PIRADS v2 grade 3 or higher on T2 and diffusion-weighted imaging and/or dynamic contrast-enhanced imaging (multiparametric MRI or mpMRI) with concordant pathology
* Tumour nodule visible on MRI occupying \<50% of prostate on any axial slice and \<50% prostate volume
* PSA \<20 ng/ml prior to starting ADT (if applicable)
* Short course (\< 6 months) concurrent androgen deprivation therapy (antiandrogens or LHRH analogues) allowed though not mandated as per the discretion of the treating physician.
* 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.

Exclusion Criteria:

* Contraindications to MRI (e.g. pacemaker, potentially mobile metal implant, claustrophobia)
* IPSS 19 or higher
* High grade disease (GG3) occult to MRI-defined lesion
* Post-void residual \>100 mls, where known
* Prostate volume \>90cc
* Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
* Unilateral or bilateral total hip replacement, or other pelvic metalwork which causes 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 excluding basal or squamous cell carcinomas of the skin, low risk non-muscle invasive bladder cancer (assuming cystoscopic follow up now negative) or small renal masses on surveillance.

Primary outcomes:
measure: Technical Feasibility
timeFrame: 4 years
Secondary outcomes:
measure: Acute and Late Toxicities
timeFrame: Upto 2 years post treatment
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Danny Vesprini, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.