NCT05705921

Standard Moderately Hypofractionated RT vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer

Recruiting now NA Last updated 20 January 2026

What this trial tests

NA trial testing Radiotherapy standard in Prostate Cancer in 484 participants. Currently enrolling.

Timeline

26 April 2023

Primary endpoint
1 January 2032

1 January 2032

Quick facts

Lead sponsor	The Netherlands Cancer Institute
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	484
Start date	26 April 2023
Primary completion	1 January 2032
Estimated completion	1 January 2032
Sites	1 location across Netherlands

Drugs / interventions tested

• Radiotherapy standard
• Radiotherapy Hypo-FLAME

Conditions studied

• Prostate Cancer — all drugs for Prostate Cancer →

Sponsor

The Netherlands Cancer Institute

Who can join

18 and older, male only, with Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

EBRT is one of the standard treatment options for patients with localized PCA. Based on the outcome of randomized trials, moderately hypofractionated RT(19-25 fractions of 2.5-3.4Gy) is considered equivalent to conventional fractionated schemes with 35-39 fractions of 2Gy. A schedule of 20 fractions to a dose of 60-62Gy is adopted as standard of care for all risk-groups. Driven by the success of moderate hypofractionation, there is a strong trend towards extreme hypofractionation, also called SBRT, reducing the number of fractions even further. The schedule mostly used is 5 fractions of 7-7.25Gy. Its effectiveness, equivalence to standard EBRT schedules, has been demonstrated for low and favourable intermediate risk (IM) patients.

For unfavourable IM (here defined as IM with ISUP grade 3) and high-risk (HR) PCA the outcome of EBRT can be further improved by dose escalation. Because of dose-limiting toxicity, the maximal dose of EBRT for conventionally fractionated schemes was approximately 80Gy. Initially hypofractionation was considered as a potential way to escalate the biologically effective dose (BED) above 80Gy, however, this proved not to be the case. With hypofractionation, a saturation in dose effect seems to be present at a BED of 80Gy. Recently, the multi-centre phase III FLAME trial broke the '80Gy barrier' and showed that in mainly HR PCA patients, treated with a conventional fractionation schedule, focal boosting of the intraprostatic lesion to a total dose of 95Gy improves biochemical disease-free survival (bDFS). However, given the advantages of hypofractionation in terms of patient comfort and costs, the FLAME schedule is not ideal as the standard treatment.

For unfavourable IM and HR PCA patients the value of SBRT has not yet been established. The FLAME trial showed that higher than standard BED is a prerequisite for optimal bDFS. Furthermore, post SBRT biopsies results suggest a dose response relationship with better outcome of dose levels above 40Gy. Therefore, probably a higher than standard dose SBRT is necessary for these patients. A recent meta-analysis suggests diminishing results from increased fraction sizes in SBRT. So, the question remains whether dose escalation in SBRT will indeed improve treatment outcome.

With standard SBRT to the whole prostate, dose escalation is limited to 40Gy because of unacceptable toxicity. In line with FLAME, we conducted the Hypo-FLAME trial investigating focal dose escalation in SBRT. In the phase II Hypo-FLAME trial, 100 patients with IM or HR PCA were treated with SBRT 35Gy in 5 weekly fractions to the whole prostate with a focal boost up to 50Gy. The acute toxicity rates, the primary endpoint, were low and similar to standard SBRT indicating this schedule can be safely applied. Given this was a phase II trial, no conclusions on oncological outcome can be drawn.

Shortening of the overall treatment time (OTT) has been suggested to play a role in SBRT efficacy and 5 fractions delivered every other day this is internationally accepted as standard. We therefore initiated the phase II Hypo-FLAME 2.0 trial, investigating the feasibility of a reduction in the OTT of the Hypo-FLAME schedule from 29 to 15 days with acute toxicity as primary endpoint. The accrual of this trial is completed and a first analysis of the primary endpoint shows low toxicity figures, well in the range of what was expected. We expect to submit the analysis for publication by the end of 2022.

At present, it is unknown what the oncological efficacy of the Hypo-FLAME schedule is compared to the standard of care in unfavourable IM and HR prostate cancer. Therefore, we will conduct a Phase III multi-centre randomized trial, in which 484 patients with unfavourable IM or HR PCA will be randomized between:

1. Standard treatment; moderately hypofractionated radiotherapy 62 Gy in 20 fractions of 3.1Gy
2. Experimental treatment; SBRT 5x7Gy with an iso-toxic integrated focal boost up to 50 Gy (Hypo-FLAME).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Automated prospective quality assurance of tumor segmentation and treatment planning in the hypo-FLAME 3.0 trial.
   Surewaard J, Bosschaert R, Beemster H, Schipaanboord B, et al · · 2026 · PMID 42208742 · DOI 10.1016/j.radonc.2026.111608
2. Efficacy of Treatments for T3bN0M0 Prostate Cancer Patients: A Systematic Review and Meta-Analysis.
   Reijnen C, Heemsbergen WD, Wever KE, Panneflek A, et al · · 2025 · PMID 40719409 · DOI 10.1002/pros.70024