Prostate Cancer
Conditions
Brief summary
This is a a randomized phase II/III trial comparing salvage SBRT with standard of care (SOC) regimens for patients with a persistent detectable PSA or biochemical progression during follow-up after radical prostatectomy.
Detailed description
This is a multicentric randomized seamless phase II/III study comparing SBRT to conventional RT or moderately hypofractionated RT on the prostate bed. All subjects will be randomly assigned in a 1:1 ratio: 1. Experimental arm: Radiotherapy treatment in 5 fractions. 2. Control arm: Radiotherapy treatment within a normofractionated or mildly hypofractionated schedule. For the control arm, each participating center can choose between a normofractionated schedule (32 to 35 treatment sessions) and a moderately hypofractionated schedule (20 sessions).
Interventions
RADIATIONStereotactic body radiotherapy (SBRT)
5 fractions of SBRT to the prostate bed with or without whole pelvic radiotherapy Treatment every other day.
RADIATIONSOC RT
Standard salvage radiotherapy to the prostate bed with or without whole pelvic radiotherapy. Each participating centre can specify upfront which RT schedule will be used in the control arm, with the choice between the following schedules: * Hypofractionated: 20 fractions (Daily treatment (OTT 4-5 weeks)) * Normofractionated: 32-35 fractions (Daily treatment (OTT 7-8 weeks))
Sponsors
Jules Bordet Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Non-inferiority randomized controlled trial
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Localized adenocarcinoma (cN0M0) of the prostate treated primarily with radical prostatectomy with definitive intent. 2. Either persistent PSA after prostatectomy (PSA ≥ 0.1 ng/mL at least 6 weeks after prostatectomy), or biochemical progression (two consecutive rising PSA amounts with a PSA \>0.1 ng/mL , or three consecutive PSA rises) 3. WHO PS 0-1 4. Age ≥18 years 5. Ability to understand and willingness to sign a study-specific informed consent prior to study entry 6. Ability to understand and answer the EPIC-26 form in one of the languages available
Exclusion criteria
1. Patients with a pT4 tumor at prostatectomy 2. Patients with previously pathologically confirmed N1 3. Patients with macroscopically involved margin at surgery (R2) 4. Patients with a history of distant metastases 5. Patients with a recurrence visible on imaging (local, pelvic, or distant). Pelvic nodes with a small diameter \>1cm and/or positive on PSMA without other explanation, are considered as a pelvic recurrence. 6. Latest PSA \> 2ng/ml 7. Patients with a IPSS \>20 8. Gleason 10 tumor 9. Prior history of high-intensity focused ultrasound ablation (HIFU), cryosurgery or brachytherapy of the prostate 10. Prior pelvic radiotherapy 11. Prior hormonal therapy started more than 6 weeks before randomization 12. History of inflammatory bowel disease, ataxia telangiectasia, prior rectal or bladder surgery. 13. Other active malignancy, except non-melanoma skin cancer, superficial bladder cancer, or malignancies with a documented disease-free survival for a minimum of 3 years before randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SBRT impact on patient-reported GI and GU symptoms | 2 years post treatment | Urinary and bowel domain of the EPIC-26 (Expanded Prostate Cancer Index Composite). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Reported Outcomes | at end of RT and following time-points counted from start of RT : 4-7 weeks (only in experimental arm), 3 months, 6 months, 1 year and yearly up to 5 years | Patient-reported outcomes according to the different * EPIC-26 domains (0-100) * IPSS score (0-35) * EQ-5D-5L scores (five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression) |
| Ccost-utility during radiotherapy | during radiotherapy | Cost-utility analysis based on EQ-5D-5L (five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression)versus costs of RT and transportation during radiotherapy |
| Physician-scored toxicity | up to 5 years | Physician-scored toxicity according to CTCAE 5.0 (grades) (Early: within 90 days; or late: 90 or more days after SBRT). Proportion of patients with G2+ toxicity will be reported specifically. |
| Blood lymphocyte evolution between study arms | 5 years | Lymphocyte count nadir relative to baseline |
| To compare biochemical progression-free survival (bPFS) to historical control and between study arms | 5 years | Biochemical progression-free survival (bPFS) |
| To compare local and regional recurrences between study arms, up to 5 years. | 5 years | Local and regional control |
| To compare Overall survival (OS) between study arms, up to 5 years. | 5 years | Overall survival (OS) |
| To compare distant metastases-free survival (dmFS) between study arms | 5 years | Distant metastases-free survival (dmFS). |
Countries
Belgium
Contacts
CONTACTRobbe Van den Begin, MD, PhD
Outcome results
None listed