A Pilot Study of Dose dE-eScalaTion IN prostATe radIOtherapy usiNg the MRL (DESTINATION)

Trial design: A single centre phase II non-randomised study

Trial population: Men with intermediate risk localised prostate cancer

Recruitment target: 20 patients in total

Trial objectives:

• Primary To develop a 5 fraction de-escalated dose SBRT protocol capable of reducing side effects

• 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 years

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 GTV plus intra-prostatic margin will receive an isotoxic 45 Gy prescription.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: De-escalated radiotherapy

Detailed Description

Primary endpoint: Technical feasibility of treating prostate cancer with toxicity- minimising radiotherapy on an MR-linac

Secondary endpoint:

• Physician reported GU and gastrointestinal (GI) toxicity (CTCAE grade) at baseline and the end of treatment then at 4 weeks and 3 months post-treatment.
• Late toxicity (CTCAE v5.0) at 1 and 2 years post-treatment
• Patient-reported outcome measures (PROMs) from the EPIC-26, IPSS, and IIEF-5 questionnaires. Patients will be asked to complete PROMs at 4 weeks, 3 and 6 months, 1 and 2 years post treatment.
• PSA control and kinetics at 2 years post-treatment

Quality of life: EPIC-26 QoL will be measured at baseline, then at 4 weeks and 3, 6, 12 and 24 months from end of treatment. IIEF-5 will be completed at baseline and months 6, 12 and 24. IPSS will be measured at all time points.

Follow-up: Patients will be assessed at 6, 12 and 24 months and then as per standard of care.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Floris Pos, MD PhD; Phone Number: +31 20 512 9111; Email: f.pos@nki.nl
• Study Contact Backup: Name: Uulke van der Heide, PhD; Phone Number: +31 20 512 9111; Email: u.vd.heide@nki.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Recruiting
    • Netherlands Cancer Institute
    • Contact: Floris Pos, MD PhD; Phone Number: +31 20 512 9111; Email: f.pos@nki.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 1, 2 or 3)
4. MRI stage T2 or less (as staged by AJCC TNM 2018)
5. MRI-visible tumour(s) of PIRADS v2 grade 3 or higher on T2 and diffusion-weighted imaging and/or dynamic contrast-enhanced imaging with concordant pathology
6. Dominant lesion <50% of prostate on any axial slice and <50% total prostate volume
7. PSA <20 ng/ml prior to starting ADT
8. Patients can be concurrently treated with androgen deprivation therapy if this would be standard of care. LHRH analogues or Bicalutamide are permitted. ADT is not mandatory where this would usually be omitted.
9. WHO Performance status 0-2
10. Ability of the participant understand and the willingness to sign a written informed consent form.
11. 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. IPSS 19 or higher
3. High grade disease (GG3) occult to MRI-defined lesion
4. Post-void residual >100 mls, where known
5. Prostate volume >90cc
6. Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
7. Unilateral or bilateral total hip replacement, or other pelvic metalwork which causes 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental radiotherapy treatment; SBRT 5x30Gy of whole prostate and isotoxic 45 Gy GTV plus intra-prostatic margin	Radiation: De-escalated radiotherapy; 5 fraction de-escalated dose SBRT protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical feasibility of treating prostate cancer with toxicity minimising radiotherapy on a MR-linac	To establish the technical feasibility of treating prostate cancer with tumour-escalated/normal prostate de-escalated dose radiotherapy on an MR-linac. Feasiblity is defined as coverage of GTV boost D90% >42Gy on the post-treatment imaging.	after 1,5 week of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute GU toxicity	Physician-reported acute GU and GI toxicity according to the CTCAE v5.0.	within 90 days after first radiation treatment
Acute GI toxicity	Physician-reported acute GU and GI toxicity according to the CTCAE v5.0.	within 90 days after first radiation treatment
Late GU toxicity	Physician-reported late GU and GI toxicity according to the CTCAE v5.0.	After at least 90 days after the first radioation treatment up to 2 years
Late GI toxicity	Physician-reported late GU and GI toxicity according to the CTCAE v5.0.	After at least 90 days after the first radioation treatment up to 2 years
PROMs	will be assessed using the International Prostate Symptom Score (IPSS) questionnaire, the EPIC-26 questionnaire and the IIEF-5 questionnaire.	2 years
Biochemical free survival	PSA control, biochemical failure/progression. Biochemical failure is defined a PSA nadir+ 2 ng/ml.	Up to 2 years

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Investigators: Principal Investigator: Floris Pos, MD PhD, The Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Prostate cancer; Radiotherapy; De-escalation; MR-Linac
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: N22DES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No