Prostate CancerNCT05705921
Standard Moderately Hypofractionated RT vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer
A study testing Radiotherapy standard and Radiotherapy Hypo-FLAME in people with Prostate Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Radiotherapy standard and Radiotherapy Hypo-FLAME
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 484 participants
- Where
- 1 siteNetherlands
- Study dates
- 26 Apr 2023to 1 Jan 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men ≥ 18 years with histologically confirmed prostate adenocarcinoma
- No evidence of lymph node or distant metastases N0M0.
- MRI visible tumor on mpMRI (PI-RADS v2 ≥ 4).
- Intermediate- or high-risk PCa, defined as at least one of the following risk criteria (note; both the clinical T-stage and imaging T stage are noted in the CRF):
- clinical stage cT2c-T3a (UICC TNM 8th edition)
- Imaging stage T2c, T3a or T3b with less than 5 mm invasion in the seminal vesicles (as defined on mp MRI)
Show all 13Show fewer
- ≥ Gleason score 4+3, (ISUP Grade groups 3,4 or 5)
- PSA ≥ 20 ng/mL
- World Health Organization (WHO) performance score ≤ 2
- International prostate symptoms score (IPSS score) < 15
- PSA ≤ 30 ng/mL
- Prostate volume ≤ 90 cc on MRI
- Ability to give written informed consent and willingness to return for follow-up
Who cannot join
- Prior pelvic radiotherapy
- TURP (transurethral prostate resection) within 6 months from start treatment
- On-line image guidance based on either fiducial markers or high-quality CBCT or MRI according to local guidelines not feasible. For example: Unsafe to have gold fiducial marker implantation, if gold fiducial markers are used for image guidance. Distorted images on MR because of hip protheses prohibit accurate MR image guidance, if MR is used for image guidance.
- Contraindications to MRI according to local hospital guidelines.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Standard Moderately Hypofractionated Radiotherapy vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer, Hypo-FLAME 3.0
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.
Read more
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:
- Standard treatment; moderately hypofractionated radiotherapy 62 Gy in 20 fractions of 3.1Gy
- Experimental treatment; SBRT 5x7Gy with an iso-toxic integrated focal boost up to 50 Gy (Hypo-FLAME).
Read the detailed description
Objective of the study:
To demonstrate superiority of whole gland SBRT with a simultaneous integrated focal boost 35/50 Gy in 5 fractions (Hypo-FLAME) regarding 5-year bDFS compared to the current standard moderately hypofractionated schedule of 62 Gy in 20 fractions of 3.1 Gy. bDFS will be assessed, using the Phoenix consensus definition.
- Conditions
- Prostate Cancer
- Being tested
- Radiotherapy standard, Radiotherapy Hypo-FLAME
- Keywords
- radiotherapy, hypofractionation, prostate cancer, stereotactic radiotherapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiotherapy standardRadiation
Standard moderately hypofractionated radiotherapy in prostate cancer
Radiotherapy Hypo-FLAMERadiation
Ultra-hypofractionated focal lesion ablative microboost in prostate cancer
| Study group | Role | What they receive |
|---|---|---|
| Standard treatment | Active comparator | moderately hypofractionated radiotherapy 62 Gy in 20 fractions of 3.1 Gy Receives: Radiation: Radiotherapy standard |
| Experimental treatment | Experimental | SBRT 5x7Gy with an iso-toxic integrated focal boost up to 50 Gy (Hypo-FLAME) in 15 days (2 fractions per week) Receives: Radiation: Radiotherapy Hypo-FLAME |
What is being measured
The primary outcome is the main question the study is designed to answer.
5-year bDFS
To demonstrate superiority of whole gland SBRT with a simultaneous integrated focal boost 35/50 Gy in 5 fractions (Hypo-FLAME) regarding 5-year freedom from biochemical (Phoenix definition) or clinical failure (recommendation of ADT >3 months after completing the neoadjuvant/adjuvant course of ADT, local recurrence, nodal recurrence or distant metastases) compared to the current standard moderately hypofractionated schedule of 62 Gy in 20 fractions of 3.1 Gy.
Measured: 5 year
Secondary outcomes (10)
Acute toxicity
Toxicity will be assessed by the gastrointestinal (GI) and genitourinary (GU) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Acute toxicity is defined as toxicity occurring within 90 days after the first radiation treatment.
Late toxicity is defined as toxicity occurring after at least 90 days after the first radiation treatment.
Measured: 3 year
Late toxicity
Toxicity will be assessed by the gastrointestinal (GI) and genitourinary (GU) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Acute toxicity is defined as toxicity occurring within 90 days after the first radiation treatment.
Late toxicity is defined as toxicity occurring after at least 90 days after the first radiation treatment.
Measured: 3 year
Patient-Reported Outcome Measures (PROMs) 1
PROMs will be assessed using the International Prostate Symptom Score (IPSS) questionnaire
Measured: 3 year
Patient-Reported Outcome Measures (PROMs) 2
PROMs will be assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26) questionnaire
Measured: 3 year
Patient-Reported Outcome Measures (PROMs) 3
PROMs will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire
Measured: 3 year
Disease-free survival
Disease-free survival defined as time from randomization until any disease progression or death from any cause.
Measured: 5 year
Distant metastases-free survival
Distant metastases-free survival defined as time from randomization until distant metastasis or death from any cause.
Measured: 5 year
Prostate cancer-specific survival
Prostate cancer-specific survival defined as time from randomization until death due to prostate cancer.
Measured: 5 year
Overall survival
Overall survival defined as time from randomization until death from any cause.
Measured: 5 year
Distant metastases-free interval
Distant metastasis-free interval, defined as time from randomization until distant metastasis.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2023
- Study start26 Apr 2023
- Primary completion1 Jan 2032 (estimated)
- Study completion1 Jan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase III multi-centre randomized trial
- Masking
- None (open label)
- Enrolment
- 484 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Floris Pos, MD PhD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05705921
- Sponsor's protocol ID
- M21HYP
- Status last verified
- Sep 2026
- First submitted
- 21 Nov 2022
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jackson WC, Silva J, Hartman HE, Dess RT, Kishan AU, Beeler WH, Gharzai LA, Jaworski EM, Mehra R, Hearn JWD, Morgan TM, Salami SS, Cooperberg MR, Mahal BA, Soni PD, Kaffenberger S, Nguyen PL, Desai N, Feng FY, Zumsteg ZS, Spratt DE. Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies. Int J Radiat Oncol Biol Phys. 2019 Jul 15;104(4):778-789. doi: 10.1016/j.ijrobp.2019.03.051. Epub 2019 Apr 6.
PubMed 30959121Widmark A, Gunnlaugsson A, Beckman L, Thellenberg-Karlsson C, Hoyer M, Lagerlund M, Kindblom J, Ginman C, Johansson B, Bjornlinger K, Seke M, Agrup M, Fransson P, Tavelin B, Norman D, Zackrisson B, Anderson H, Kjellen E, Franzen L, Nilsson P. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet. 2019 Aug 3;394(10196):385-395. doi: 10.1016/S0140-6736(19)31131-6. Epub 2019 Jun 18.
PubMed 31227373Vogelius IR, Bentzen SM. Dose Response and Fractionation Sensitivity of Prostate Cancer After External Beam Radiation Therapy: A Meta-analysis of Randomized Trials. Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):858-865. doi: 10.1016/j.ijrobp.2017.12.011. Epub 2017 Dec 15.
PubMed 29485063Kerkmeijer LGW, Groen VH, Pos FJ, Haustermans K, Monninkhof EM, Smeenk RJ, Kunze-Busch M, de Boer JCJ, van der Voort van Zijp J, van Vulpen M, Draulans C, van den Bergh L, Isebaert S, van der Heide UA. Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):787-796. doi: 10.1200/JCO.20.02873. Epub 2021 Jan 20.
PubMed 33471548Zelefsky MJ, Goldman DA, Reuter V, Kollmeier M, McBride S, Zhang Z, Varghese M, Pei X, Fuks Z. Long-Term Implications of a Positive Posttreatment Biopsy in Patients Treated with External Beam Radiotherapy for Clinically Localized Prostate Cancer. J Urol. 2019 Jun;201(6):1127-1133. doi: 10.1097/JU.0000000000000110.
PubMed 30741847Zelefsky MJ, Goldman DA, Hopkins M, Pinitpatcharalert A, McBride S, Gorovets D, Ehdaie B, Fine SW, Reuter VE, Tyagi N, Happersett L, Teyateeti A, Zhang Z, Kollmeier MA. Predictors for post-treatment biopsy outcomes after prostate stereotactic body radiotherapy. Radiother Oncol. 2021 Jun;159:33-38. doi: 10.1016/j.radonc.2021.02.008. Epub 2021 Feb 13.
PubMed 33587971Vogelius IR, Bentzen SM. Diminishing Returns From Ultrahypofractionated Radiation Therapy for Prostate Cancer. Int J Radiat Oncol Biol Phys. 2020 Jun 1;107(2):299-304. doi: 10.1016/j.ijrobp.2020.01.010. Epub 2020 Jan 25.
PubMed 31987958Quon HC, Ong A, Cheung P, Chu W, Chung HT, Vesprini D, Chowdhury A, Panjwani D, Pang G, Korol R, Davidson M, Ravi A, McCurdy B, Zhang L, Mamedov A, Deabreu A, Loblaw A. Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial. Radiother Oncol. 2018 May;127(2):206-212. doi: 10.1016/j.radonc.2018.02.029. Epub 2018 Mar 15.
PubMed 29551231Kim DW, Cho LC, Straka C, Christie A, Lotan Y, Pistenmaa D, Kavanagh BD, Nanda A, Kueplian P, Brindle J, Cooley S, Perkins A, Raben D, Xie XJ, Timmerman RD. Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014 Jul 1;89(3):509-17. doi: 10.1016/j.ijrobp.2014.03.012.
PubMed 24929162Draulans C, van der Heide UA, Haustermans K, Pos FJ, van der Voort van Zyp J, De Boer H, Groen VH, Monninkhof EM, Smeenk RJ, Kunze-Busch M, De Roover R, Depuydt T, Isebaert S, Kerkmeijer LGW. Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer. Radiother Oncol. 2020 Jun;147:92-98. doi: 10.1016/j.radonc.2020.03.015. Epub 2020 Apr 1.
PubMed 32247206Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):965-74. doi: 10.1016/j.ijrobp.2006.04.029.
PubMed 16798415Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, Rouviere O, Logager V, Futterer JJ; European Society of Urogenital Radiology. ESUR prostate MR guidelines 2012. Eur Radiol. 2012 Apr;22(4):746-57. doi: 10.1007/s00330-011-2377-y. Epub 2012 Feb 10.
PubMed 22322308van Schie MA, Dinh CV, Houdt PJV, Pos FJ, Heijmink SWTJP, Kerkmeijer LGW, Kotte ANTJ, Oyen R, Haustermans K, van der Heide UA. Contouring of prostate tumors on multiparametric MRI: Evaluation of clinical delineations in a multicenter radiotherapy trial. Radiother Oncol. 2018 Aug;128(2):321-326. doi: 10.1016/j.radonc.2018.04.015. Epub 2018 May 3.
PubMed 29731160Salembier C, Villeirs G, De Bari B, Hoskin P, Pieters BR, Van Vulpen M, Khoo V, Henry A, Bossi A, De Meerleer G, Fonteyne V. ESTRO ACROP consensus guideline on CT- and MRI-based target volume delineation for primary radiation therapy of localized prostate cancer. Radiother Oncol. 2018 Apr;127(1):49-61. doi: 10.1016/j.radonc.2018.01.014.
PubMed 29496279Gladwish A, Pang G, Cheung P, D'Alimonte L, Deabreu A, Loblaw A. Prostatic displacement during extreme hypofractionated radiotherapy using volumetric modulated arc therapy (VMAT). Radiat Oncol. 2014 Nov 28;9:262. doi: 10.1186/s13014-014-0262-y.
PubMed 25430973
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Standard Moderately Hypofractionated Radiotherapy vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer, Hypo-FLAME 3.0
- ClinicalTrials.gov ID
- NCT05705921
- Acronym / sponsor ID
- M21HYP
- Conditions
- Prostate Cancer
- Keywords
- radiotherapy, hypofractionation, prostate cancer, stereotactic radiotherapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 484 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, Universitaire Ziekenhuizen KU Leuven
- Study start
- 26 Apr 2023 (actual)
- Primary completion
- 1 Jan 2032 (estimated)
- Study completion
- 1 Jan 2032 (estimated)
- First posted
- 31 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Standard treatment; moderately hypofractionated radiotherapy 62 Gy in 20 fractions of 3.1Gy
- Experimental treatment; SBRT 5x7Gy with an iso-toxic integrated focal boost up to 50 Gy (Hypo-FLAME).
Detailed description
Objective of the study:
To demonstrate superiority of whole gland SBRT with a simultaneous integrated focal boost 35/50 Gy in 5 fractions (Hypo-FLAME) regarding 5-year bDFS compared to the current standard moderately hypofractionated schedule of 62 Gy in 20 fractions of 3.1 Gy. bDFS will be assessed, using the Phoenix consensus definition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase III multi-centre randomized trial
| Arm | Type | Receives |
|---|---|---|
| Standard treatment | Active comparator | Radiation: Radiotherapy standardmoderately hypofractionated radiotherapy 62 Gy in 20 fractions of 3.1 Gy |
| Experimental treatment | Experimental | Radiation: Radiotherapy Hypo-FLAMESBRT 5x7Gy with an iso-toxic integrated focal boost up to 50 Gy (Hypo-FLAME) in 15 days (2 fractions per week) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Men ≥ 18 years with histologically confirmed prostate adenocarcinoma
- No evidence of lymph node or distant metastases N0M0.
- MRI visible tumor on mpMRI (PI-RADS v2 ≥ 4).
- Intermediate- or high-risk PCa, defined as at least one of the following risk criteria (note; both the clinical T-stage and imaging T stage are noted in the CRF):
- World Health Organization (WHO) performance score ≤ 2
Key exclusion criteria (4 listed)
- Prior pelvic radiotherapy
- TURP (transurethral prostate resection) within 6 months from start treatment
- On-line image guidance based on either fiducial markers or high-quality CBCT or MRI according to local guidelines not feasible. For example: Unsafe to have gold fiducial marker implantation, if gold fiducial markers are used for image guidance. Distorted images on MR because of hip protheses prohibit accurate MR image guidance, if MR is used for image guidance.
- Contraindications to MRI according to local hospital guidelines.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radiotherapy standardStandard moderately hypofractionated radiotherapy in prostate cancer | Radiation | Standard treatment |
| Radiotherapy Hypo-FLAMEUltra-hypofractionated focal lesion ablative microboost in prostate cancer | Radiation | Experimental treatment |
Primary outcome
5-year bDFS
Time frame: 5 year
To demonstrate superiority of whole gland SBRT with a simultaneous integrated focal boost 35/50 Gy in 5 fractions (Hypo-FLAME) regarding 5-year freedom from biochemical (Phoenix definition) or clinical failure (recommendation of ADT >3 months after completing the neoadjuvant/adjuvant course of ADT, local recurrence, nodal recurrence or distant metastases) compared to the current standard moderately hypofractionated schedule of 62 Gy in 20 fractions of 3.1 Gy.
10 secondary outcomes
Acute toxicity
Time frame: 3 year
Late toxicity
Time frame: 3 year
Patient-Reported Outcome Measures (PROMs) 1
Time frame: 3 year
Patient-Reported Outcome Measures (PROMs) 2
Time frame: 3 year
Patient-Reported Outcome Measures (PROMs) 3
Time frame: 3 year
Disease-free survival
Time frame: 5 year
Distant metastases-free survival
Time frame: 5 year
Prostate cancer-specific survival
Time frame: 5 year
Overall survival
Time frame: 5 year
Distant metastases-free interval
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Background: PubMed 30959121Jackson WC, Silva J, Hartman HE, Dess RT, Kishan AU, Beeler WH, Gharzai LA, Jaworski EM, Mehra R, Hearn JWD, Morgan TM, Salami SS, Cooperberg MR, Mahal BA, Soni PD, Kaffenberger S, Nguyen PL, Desai N, Feng FY, Zumsteg ZS, Spratt DE. Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies. Int J Radiat Oncol Biol Phys. 2019 Jul 15;104(4):778-789. doi: 10.1016/j.ijrobp.2019.03.051. Epub 2019 Apr 6.
- Background: PubMed 31227373Widmark A, Gunnlaugsson A, Beckman L, Thellenberg-Karlsson C, Hoyer M, Lagerlund M, Kindblom J, Ginman C, Johansson B, Bjornlinger K, Seke M, Agrup M, Fransson P, Tavelin B, Norman D, Zackrisson B, Anderson H, Kjellen E, Franzen L, Nilsson P. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet. 2019 Aug 3;394(10196):385-395. doi: 10.1016/S0140-6736(19)31131-6. Epub 2019 Jun 18.
- Background: PubMed 29485063Vogelius IR, Bentzen SM. Dose Response and Fractionation Sensitivity of Prostate Cancer After External Beam Radiation Therapy: A Meta-analysis of Randomized Trials. Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):858-865. doi: 10.1016/j.ijrobp.2017.12.011. Epub 2017 Dec 15.
- Background: PubMed 33471548Kerkmeijer LGW, Groen VH, Pos FJ, Haustermans K, Monninkhof EM, Smeenk RJ, Kunze-Busch M, de Boer JCJ, van der Voort van Zijp J, van Vulpen M, Draulans C, van den Bergh L, Isebaert S, van der Heide UA. Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):787-796. doi: 10.1200/JCO.20.02873. Epub 2021 Jan 20.
- Background: PubMed 30741847Zelefsky MJ, Goldman DA, Reuter V, Kollmeier M, McBride S, Zhang Z, Varghese M, Pei X, Fuks Z. Long-Term Implications of a Positive Posttreatment Biopsy in Patients Treated with External Beam Radiotherapy for Clinically Localized Prostate Cancer. J Urol. 2019 Jun;201(6):1127-1133. doi: 10.1097/JU.0000000000000110.
- Background: PubMed 33587971Zelefsky MJ, Goldman DA, Hopkins M, Pinitpatcharalert A, McBride S, Gorovets D, Ehdaie B, Fine SW, Reuter VE, Tyagi N, Happersett L, Teyateeti A, Zhang Z, Kollmeier MA. Predictors for post-treatment biopsy outcomes after prostate stereotactic body radiotherapy. Radiother Oncol. 2021 Jun;159:33-38. doi: 10.1016/j.radonc.2021.02.008. Epub 2021 Feb 13.
- Background: PubMed 31987958Vogelius IR, Bentzen SM. Diminishing Returns From Ultrahypofractionated Radiation Therapy for Prostate Cancer. Int J Radiat Oncol Biol Phys. 2020 Jun 1;107(2):299-304. doi: 10.1016/j.ijrobp.2020.01.010. Epub 2020 Jan 25.
- Background: PubMed 29551231Quon HC, Ong A, Cheung P, Chu W, Chung HT, Vesprini D, Chowdhury A, Panjwani D, Pang G, Korol R, Davidson M, Ravi A, McCurdy B, Zhang L, Mamedov A, Deabreu A, Loblaw A. Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial. Radiother Oncol. 2018 May;127(2):206-212. doi: 10.1016/j.radonc.2018.02.029. Epub 2018 Mar 15.
- Background: PubMed 24929162Kim DW, Cho LC, Straka C, Christie A, Lotan Y, Pistenmaa D, Kavanagh BD, Nanda A, Kueplian P, Brindle J, Cooley S, Perkins A, Raben D, Xie XJ, Timmerman RD. Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014 Jul 1;89(3):509-17. doi: 10.1016/j.ijrobp.2014.03.012.
- Background: PubMed 32247206Draulans C, van der Heide UA, Haustermans K, Pos FJ, van der Voort van Zyp J, De Boer H, Groen VH, Monninkhof EM, Smeenk RJ, Kunze-Busch M, De Roover R, Depuydt T, Isebaert S, Kerkmeijer LGW. Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer. Radiother Oncol. 2020 Jun;147:92-98. doi: 10.1016/j.radonc.2020.03.015. Epub 2020 Apr 1.
- Background: PubMed 16798415Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):965-74. doi: 10.1016/j.ijrobp.2006.04.029.
- Background: PubMed 22322308Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, Rouviere O, Logager V, Futterer JJ; European Society of Urogenital Radiology. ESUR prostate MR guidelines 2012. Eur Radiol. 2012 Apr;22(4):746-57. doi: 10.1007/s00330-011-2377-y. Epub 2012 Feb 10.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Floris Pos, MD PhD principal investigator
The Netherlands Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Radiotherapy standard and Radiotherapy Hypo-FLAME in people with Prostate Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
5-year bDFS (time frame: 5 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05705921, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.