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Trial Title:
Standard Moderately Hypofractionated RT vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer
NCT ID:
NCT05705921
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Conditions: Keywords:
radiotherapy
hypofractionation
prostate cancer
stereotactic radiotherapy
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Phase III multi-centre randomized trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Radiotherapy standard
Description:
Standard moderately hypofractionated radiotherapy in prostate cancer
Arm group label:
Standard treatment
Intervention type:
Radiation
Intervention name:
Radiotherapy Hypo-FLAME
Description:
Ultra-hypofractionated focal lesion ablative microboost in prostate cancer
Arm group label:
Experimental treatment
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. 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).
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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)
- ≥ 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
Exclusion Criteria:
- 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.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Netherlands Cancer Institute
Address:
City:
Amsterdam
Zip:
1066 CX
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Floris Pos, MD
Phone:
+31205129111
Email:
f.pos@nki.nl
Start date:
April 26, 2023
Completion date:
January 1, 2032
Lead sponsor:
Agency:
The Netherlands Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Radboud University Medical Center
Agency class:
Other
Collaborator:
Agency:
Universitaire Ziekenhuizen KU Leuven
Agency class:
Other
Source:
The Netherlands Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05705921