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

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

NCT ID: NCT06518226

Condition: Prostate Cancer
Prostate Adenocarcinoma
Localized Prostate Carcinoma

Conditions: Official terms:
Prostatic Neoplasms

Conditions: Keywords:
MR-guided adaptive radiotherapy
MRgRT
Quality of life
Patient-reported outcomes
Ultrahypofractionation

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: Randomized controlled trial

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Ultrahypofractionated MRgRT in 2 fractions
Description: 2x12 Gy with boost to GTV up to 13.5 Gy
Arm group label: Ultrahypofractionated MRgRT in 2 fractions

Intervention type: Radiation
Intervention name: Standard of care: MRgRT in 5 fractions
Description: 5x7.25 Gy
Arm group label: Standard of care: MRgRT in 5 fractions

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.

Criteria for 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

Gender: Male

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University Medical Center Utrecht

Address:
City: Utrecht
Zip: 3584 CX
Country: Netherlands

Status: Recruiting

Contact:
Last name: Tariq A Lalmahomed, MD

Phone: +31 (0)887574536
Email: t.a.lalmahomed-2@umcutrecht.nl

Contact backup:
Last name: Jochem R.N. Van der Voort van Zyp, MD PhD
Email: j.r.n.vandervoortvanzyp@umcutrecht.nl

Investigator:
Last name: Jochem RN Van der Voort van Zyp, MD PhD
Email: Principal Investigator

Start date: March 28, 2024

Completion date: February 1, 2031

Lead sponsor:
Agency: UMC Utrecht
Agency class: Other

Source: UMC Utrecht

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06518226