Ignite Creation Date:
2024-05-06 @ 6:33 PM
Last Modification Date:
2024-10-26 @ 2:50 PM
Study NCT ID:
NCT05705921
Status:
RECRUITING
Last Update Posted:
2024-06-07
First Post:
2022-11-21
Brief Title:
Standard Moderately Hypofractionated RT vs Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer
Sponsor:
The Netherlands Cancer Institute
Organization:
The Netherlands Cancer Institute
Study Overview
Official Title:
Standard Moderately Hypofractionated Radiotherapy vs Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer Hypo-FLAME 30
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
EBRT is one of the standard treatment options for patients with localized PCA Based on the outcome of randomized trials moderately hypofractionated RT19-25 fractions of 25-34Gy 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 7-725Gy 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 20 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 31Gy
2 Experimental treatment SBRT 5x7Gy with an iso-toxic integrated focal boost up to 50 Gy Hypo-FLAME
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 20 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 31Gy
2 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 3550 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 31 Gy bDFS will be assessed using the Phoenix consensus definition
To demonstrate superiority of whole gland SBRT with a simultaneous integrated focal boost 3550 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 31 Gy bDFS will be assessed using the Phoenix consensus definition
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None