Two-Fraction Ultrahypofractionated Radiotherapy With Focal Boost for Intermediate Risk, Localized Prostate Cancer

NCT ID: NCT06518226

Last Updated: 2024-07-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-28
• Study Completion Date: 2031-02-01

Brief Summary

The goal of this clinical trial is to assess the non-inferiority irradiating low and intermediate risk, localized prostate cancer in two fractions of radiotherapy, compared to five fractions of radiotherapy which is the standard of care. The main question it aims to answer are:

• Do participants in the interventional arm have more physician-reported grade 2 or higher acute Common Terminology Criteria for Adverse Events (CTCAE) genitourinary (GU) side effects?

Participants in the intervention arm will receive two fractions of radiotherapy, in which the prostate is irradiated with 12 Gy per fraction and the tumor receives a boost of up to 13.5 Gray (Gy), over the course of 8 days. Those in the control arm will receive five fractions of radiotherapy of 7.25 Gy each to the prostate, without a boost to the tumor, over the course of 16-18 days.

Detailed Description

Rationale: Hypofractionation in prostate cancer radiotherapy has already led to a drastic reduction in fractionation scheme from 35 fractions to the now standard 5 fractions for patients with intermediate risk prostate cancer. Currently, biochemical progression free survival is at approximately 90% at five-year follow-up for intermediate risk prostate cancer patients, which leaves little to no room for further improvement in oncological outcomes. However, with an ageing population and a subsequently higher volume of patients with localized prostate cancer, there is a need to improve and optimize current treatment options. Treatment cost within the field of prostate oncology will further increase over the years to come, and an early economic health evaluation has demonstrated that a 2-fractionation scheme with MRI-guided radiotherapy (MRgRT) for intermediate risk prostate cancer patients is cost effective compared to the standard of care 5 fractions scheme.

Previous research demonstrated the feasibility of delivering high doses of radiation in only two fractions, both in silico as well as in a clinical setting using a conventional CT-guided linear accelerator. With the introduction of MRgRT, however, it has become possible to deliver higher doses of radiation with more accuracy, while limiting genitourinary (GU) and gastrointestinal (GI) toxicity. This leads us to believe that improvements can be made both in terms of costs as well as patient reported quality of life.

Objective: To assess the effectiveness, safety and feasibility of treating patients with localized, intermediate risk prostate cancer who will receive radiation therapy in two fractions of 12 Gy with a boost to the gross tumor volume of 13.5 Gy per fraction in 8 days, as compared to standard care (36.25 Gy in five fractions in 16-18 days), on an ELEKTA Unity MR-Linac system.

Study design: Single-center, prospective, open label, phase II randomized controlled trial.

Study population: Men with localized, intermediate risk prostate cancer who are to receive radiation therapy with curative intent. Exclusion criteria are previous radical prostatectomy, presence of contraindications for MRI or conditions which predispose to increased morbidity and/or toxicity (such as colitis ulcerosa, Crohn's disease), previous pelvic radiotherapy, metal pelvic implants causing artefact of MR-imaging, and previous invasive malignancy within the last 5 year (excluding cutaneous basal cell carcinoma)

Intervention: Participants in the intervention arm will receive two fractions of 12 Gy to the clinical target volume (CTV) with a boost up to 13.5 Gy to the gross tumor volume (GTV) of radiation in a time span of 8 days on an MR-linac. Those in the control arm will receive five fractions of 7.25 Gy in a time span of 16-18 days on an MR-linac, as per standard care.

Main study parameters/endpoints: Difference in proportion of participants with acute CTCAE grade 2 or higher GU toxicity.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This trial will be nested in the observational Multiple OutcoMe EvaluatioN of radiation Therapy Using the MR-Linac (MOMENTUM) study, and participants will receive QOL questionnaires which are already embedded within this cohort. Therefore, participants are not subjected to an additional burden during the course and follow-up period of this study. In a recently published study, there was no evidence that hypofractionation caused more GU and/or GI grade ≥2 toxicity. Radiobiologically, the low alpha/beta ratio of prostate cancer makes it more sensitive to higher doses of radiation in fewer fractions, which is in fact the essence of the ultrahypofractionation scheme that we offer in the interventional arm.

Conditions

Prostate Cancer; Prostate Adenocarcinoma; Localized Prostate Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ultrahypofractionated MRgRT in 2 fractions

MRgRT to the prostate in 2 fractions of 12 Gy, with a focal boost of 13.5 Gy to the gross tumor volume (GTV), administered over the course of 8 days.

Group Type: EXPERIMENTAL

Ultrahypofractionated MRgRT in 2 fractions

Intervention Type: RADIATION

2x12 Gy with boost to GTV up to 13.5 Gy

Standard of care: MRgRT in 5 fractions

MRgRT to the prostate in 5 fractions of 7.25 Gy to the prostate without focal boost, administered over the course of 16-18 days.

Group Type: ACTIVE_COMPARATOR

Standard of care: MRgRT in 5 fractions

Intervention Type: RADIATION

5x7.25 Gy

Interventions

Ultrahypofractionated MRgRT in 2 fractions

2x12 Gy with boost to GTV up to 13.5 Gy

Intervention Type: RADIATION

Standard of care: MRgRT in 5 fractions

5x7.25 Gy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years
• Histopathological confirmation of prostate adenocarcinoma requiring radical treatment
• European Association of Urology (EAU) intermediate risk prostate cancer, defined as Prostate Specific Antigen (PSA) level of < 20 ng/ml, Gleason score ≤ 7, cT1c-cT2b/iT3a (non-bulky, < 20mm)
• Written informed consent
• Ability and willingness to comply with Patient Reported Outcome Measure (PROM) questionnaires schedule throughout the study
• Inclusion in the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-Linac Study (MOMENTUM)

Exclusion Criteria

• Contraindications to MRI
• International Prostate Symptom Score (IPSS) of 15 or higher
• Prostate volume > 80 cc
• Comorbidities which predispose to significant toxicity (e.g., inflammatory bowel disease)
• Metal pelvic implants which cause artefact on MR-imaging sequences
• Previous radical prostatectomy
• Previous pelvic radiotherapy
• Previous invasive malignancy within the last 5 years, excluding basal cell carcinoma of the skin

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

J.R.N. van der Voort van Zyp

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Tariq A. Lalmahomed, MD

Role: CONTACT

t.a.lalmahomed-2@umcutrecht.nl

+31 (0)887574536

Facility Contacts

Tariq A Lalmahomed, MD

Role: primary

t.a.lalmahomed-2@umcutrecht.nl

+31 (0)887574536

Jochem R.N. Van der Voort van Zyp, MD PhD

Role: backup

j.r.n.vandervoortvanzyp@umcutrecht.nl

References

Westley RL, Biscombe K, Dunlop A, Mitchell A, Oelfke U, Nill S, Murray J, Pathmanathan A, Hafeez S, Parker C, Ratnakumaran R, Alexander S, Herbert T, Hall E, Tree AC. Interim Toxicity Analysis From the Randomized HERMES Trial of 2- and 5-Fraction Magnetic Resonance Imaging-Guided Adaptive Prostate Radiation Therapy. Int J Radiat Oncol Biol Phys. 2024 Mar 1;118(3):682-687. doi: 10.1016/j.ijrobp.2023.09.032. Epub 2023 Sep 29.

Reference Type: BACKGROUND

PMID: 37776979 (View on PubMed)

Other Identifiers

NL85364.041.23

Identifier Type: -

Identifier Source: org_study_id