Clinical trial NCT06638541: Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions
Official title: Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions - a Randomised Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Keywords: De-escalation
Radiotherapy
MR-Linac
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Elekta Limited
name: MRL Consortium
First posted: 2024-10-15
Enrollment: 54
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: Inclusion Criteria:

1. Men aged ≥18 years
2. Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy
3. Gleason score 3+3, 3+4 or 4+3 (Grade groups (GG) 1, 2 or 3)
4. MRI stage T3a or less (as staged by AJCC TNM 2018). MRI must be performed within a year of randomisation
5. 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
6. The MRI-defined lesion must be confirmed as malignant on biopsies (Gleason grade must be within the limits expressed in inclusion factor 3)
7. 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.
8. PSA \<20 ng/ml prior to starting ADT, if used
9. WHO Performance status 0-2
10. Ability of the participant understand and the willingness to sign a written informed consent form.
11. Willing to consent to contraception during and for 1 year after treatment when applicable.
12. Ability/willingness to comply with the patient reported outcome questionnaires schedule throughout the study.

Exclusion Criteria:

1. Contraindications to MRI (e.g. pacemaker, potentially mobile metal implant, claustrophobia)
2. Severe GU symptoms that would preclude extreme hypofractionation per the discretion of the treating physician.
3. IPSS Score \> 19
4. 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.
5. Prostate volume \>90cc
6. Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
7. Hip replacement, or other pelvic metalwork which causes significant artefact on diffusion-weighted imaging
8. Previous pelvic radiotherapy
9. Patients needing \>6 months of ADT due to disease parameters.
10. 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.
11. Participating in another interventional trial for prostate cancer

Primary outcomes:
measure: Acute GU toxicity
timeFrame: 12 weeks
Secondary outcomes:
measure: Acute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) toxicity
timeFrame: Baseline, last fraction, week 2, 4 and 12
measure: Late Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) toxicity
timeFrame: Month 6, 12, 24
measure: Feasibility of radiation delivery
timeFrame: At time of treatment
measure: Dosimetry
timeFrame: At time of treatment
measure: Patient reported outcome measures
timeFrame: Baseline, last fraction of treatment, week 2, 4 and 12, 6 months, 1 and 2 years post treatment.
measure: Patient reported outcome measures
timeFrame: Baseline, 4 and 12 weeks, 6 months, 1 and 2 years post treatment.
measure: Patient reported outcome measures
timeFrame: Baseline, 6 months, 1 and 2 years post treatment.
measure: PSA kinetics
timeFrame: Baseline (pre ADT), week 12, month 6, and 1 and 2 years post treatment
Other outcomes:
Locations:
Study officials:
affiliation: Royal Marsden Hospital, Institute of Cancer Research
name: Alison Tree
role: STUDY_CHAIR
References: