Image-guided Focal Dose Escalation- Primary pc Treated With Primary External Beam Hypofract.Stereotactic rt

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT06330909

Studienbeginn:
August 2022

Letztes Update:
26.03.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Prostatic Neoplasms

Geschlecht:
Männer

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
University Hospital Freiburg

Collaborator:
German Federal Ministry of Education and Research

Studienleiter

Anca-Ligia Grosu, Prof.
Study Chair
Medical Center- University of Freiburg

Kontakt

Sabine Schneider-Fuchs, DR
Kontakt:
Phone: +4976127074040
E-Mail: sabine.schneider-fuchs@uniklinik-freiburg.de» Kontaktdaten anzeigen

Sonja Adebahr, MD
Kontakt:
Phone: +4976127095200
E-Mail: sonja.adebahr@uniklinik-freiburg.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Medical Center - University of Freiburg
79106 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Studien-Informationen

Detailed Description:

Prostate cancer (PCa) is the most frequent diagnosed malignancy in male patients in Europe

and radiation therapy (RT) is a main treatment option. Conventional RT for patients with

primary PCa aims at delivering a homogeneous dose to the entire prostatic gland. However,

recent studies proved that modern medical imaging is able to detect accurately the

intraprostatic tumour mass (ITM). Consequently, RT concepts for PCa have an imminent need to

be rectified in order to individualize the RT strategy by considering the individual tumor

localization. In addition, the radiobiological characteristics of the major organs at risk,

the rectum and urinary bladder / urethra, as well as of the PCa itself speak for clear

advantages of hypofractionated radiation therapy. High-precision stereotactic body radiation

therapy (SBRT) significantly shortens the duration of treatment, with clear implications for

quality of life and socio-economic aspects.

The aim of this prospective, randomized, multicenter phase III study is the personalization

of RT for patients with primary PCa based on individual tumor geometry derived from modern

imaging techniques (mpMRI and PSMA-PET/CT). In the experimental (arm A) simultaneous RT dose

escalation to the ITM will be performed under strict adherence to the organs at risks' dose

constraints by using SBRT (ultra-hypofractionated radiation therapy) in a shorter treatment

time (5 fractions vs. 20 fractions). In the control arm (arm B) the entire prostatic gland

will receive a homogeneous moderately hypofractionated RT according to the current

guidelines. RFS after RT (calculated from randomization) will be assessed as the primary

endpoint as well as toxicities and patient reported quality of life as secondary endpoints.

For the patients in the experimental arm we expect a significant benefit in relapse free

survival (from 80% to 90% at 5 years). The improvement in relapse free survival could

increase the metastatic free survival, prostate cancer survival and overall survival in high

risk PCa patients. Considering the epidemiological importance of the PCa these results could

have a significant socio-economic impact. In parallel a translational research program will

address the identification of novel biomarkers/bio-imaging-markers predictive for outcome

after RT. Furthermore, involvement of patient representatives includes information about the

studies status and contributes to patient empowerment. These aspects will facilitate the

evolution from an individualized RT to a personalized RT.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the prostate (histological confirmation can

be based on tissue taken at any time, but a re-biopsy should be considered if the

biopsy is more than 12 months old)

2. Primary localized PCa (cN0 and cM0 in mpMRI and PSMA PET):

- high- or very high-risk according to NCCN v2.2021 (see 20.3) OR

- unfavorable intermediate-risk disease according to NCCN v2.2021 (see 20.3)

3. Signed, written informed consent for HypoFocal-SBRT study

4. Age > 18 years

5. Previously conducted PSMA-PET/CT and mpMRI scans or PSMA-PET/MR, fulfilling standard

requirements for PCa (see also 6.5)

6. ECOG Performance score 0 or 1

7. IPSS Score ≤15

8. Prostate volume ≤75 ml at RT planning

Exclusion Criteria:

1. Evidence of neuroendocrine tumor cells

2. Prior radiotherapy to the prostate or pelvis

3. Prior radical prostatectomy

4. Prior focal therapy approaches to the prostate

5. Time gap between the beginning of ADT and conduction of mpMRI and PSMA PET scans is >1

month

6. Radiologically suspicious or pathologically confirmed lymph node involvement (cN+) in

mpMRI and/or PSMA PET/CT

7. Evidence of metastatic disease (cM+) in mpMRI and/or PSMA PET/CT

8. Evidence of cT4 disease in mpMRI or PSMA PET/CT

9. PSA >30 ng/ml prior to starting ADT

10. Expected patient survival <5 years

11. Bilateral hip prostheses or any other implants/hardware that would introduce

substantial CT artefacts

12. Contraindication to undergo a mpMRI scan

13. Prostate surgery (TURP or HOLEP) with a significant tissue cavity or prostate surgery

(TURP or HOLEP) within the last 6 months prior to randomization

14. Medical conditions likely to make radiotherapy inadvisable e.g. acute inflammatory

bowel disease, hemiplegia or paraplegia

15. Previous malignancy within the last 2 years (except basal cell carcinoma or squamous

cell carcinoma of the skin), or if previous malignancy is expected to significantly

compromise 5 year survival

16. Any other contraindication to external beam radiotherapy (EBRT) to the pelvis

17. In mpMRI and PSMA PET/CT or PSMA PET/MRI scans no visible tumor

18. Participation in any other interventional clinical trial within the last 30 days

before the start of this trial

19. Simultaneous participation in other interventional trials which could interfere with

this trial; simultaneous participation in registry and diagnostic trials is allowed

20. Patient without legal capacity who is unable to understand the nature, significance

and consequences of the trial;

21. Known or persistent abuse of medication, drugs or alcohol

22. Patients expected to have severe set up problems

23. Dose constraints for organs at risk cannot be adhered to

Studien-Rationale

Primary outcome:

1. Relapse free survival (Time Frame - 7 years):
Primary endpoint is relapse free survival (RFS), defined as time from randomization to relapse or death. Relapse free survival times will be censored at the time see last alive without relapse. Analysis will be conducted after finalization of the study.

Secondary outcome:

1. Time to local failure after randomization (Time Frame - 7 years):
Time to local failure after randomization. Local recurrences have to be confirmed by biopsy

2. Metastatic free survival after randomization (Time Frame - 7 years):
Metastatic free survival after randomization (all metastases have to be confirmed by imaging, preferably PSMA-PET/CT or mpMR imaging)

3. Overall (OS) and prostate cancer specific (PCSS) survival after randomization (Time Frame - 7 years):
Overall (OS) and prostate cancer specific (PCSS) survival after randomization

4. Time to biochemical failure (phoenix definition) after randomization (Time Frame - 7 years):
Time to biochemical failure (phoenix definition) after randomization

5. Patient reported acute quality of life (QOL) - Expanded Prostate Index Composite-26 (EPIC-26) (Time Frame - at months 3 and 6 after randomization):
Patient reported acute quality of life (QOL). Acute QOL will be assessed with the Expanded Prostate Index Composite-26 (EPIC-26) Short Form and International Prostate Symptom Score (IPSS) questionnaires at the following time points: before treatment (baseline), last day of treatment, FU visits at months 3 and 6 after randomization

6. Patient reported late quality of life (QOL) (Time Frame - up to 90 after randomization):
Patient reported late quality of life (QOL). Late QOL will be assessed with the Expanded Prostate Index Composite-26 (EPIC-26) Short Form and International Prostate Symptom Score (IPSS) questionnaires at the following time points: FU visits at months 9,12,15,18 21, 24, 30, 36, 42, 48 and months 54, 60, 66, 72, 78, 84 up to 90 after randomization

7. Cumulative acute GU and GI toxicities during and up to 3 months after RT using the CTCAEv5.0 criteria (Time Frame - up to 3 months):
Cumulative acute GU and GI toxicities during and up to 3 months after RT using the CTCAEv5.0 criteria

8. Cumulative Chronic GU and GI toxicities after RT using the CTCAEv5.0 criteria (Time Frame - 7 years):
Cumulative Chronic GU and GI toxicities after RT using the CTCAEv5.0 criteria

9. Dose constraints and prescription doses / recruited patients (Time Frame - 7 years):
Feasibility and adherence to dose constraints by measuring the ratio between: number of patients with fulfilled dose constraints and prescription doses / recruited patients

10. Characterization of safety: adverse events (Time Frame - 7 years):
Characterization of safety: adverse events

Studien-Arme

Experimental: Arm A - IMRT/IGRT/SBRT
Prostate and seminal vesicles RT with 30 Gy in 6 Gy / fraction; prostate RT with 35 Gy in 7 Gy / fraction including a simultaneous integrated boost (SIB) on the intraprostatic tumour mass (ITM) with 40- 42 Gy in 8 - 8.4 Gy / fraction. If the boost volume is ≥10 ml and/ or ≥ 1/3 of the prostate, the SIB on the ITM has to be restrained to 40 Gy in 8 Gy / fraction. SBRT will be performed twice a week, with at least 2 days between two RT fractions, 5 fractions in 3 weeks (technique: IMRT/IGRT/SBRT).
Active Comparator: Arm B - IMRT/IGRT
Prostate and seminal vesicles RT with 46.4 Gy in 2.32 Gy per fraction, prostate RT with 60 and 62 Gy in 3 and 3.1 Gy per fraction for unfavorable intermediate-risk and high-risk patients, respectively, 20 fractions, 5 fractions /week, (technique: IMRT/IGRT).

Geprüfte Regime

Radiotherapy (RT) Arm A - IMRT/IGRT/SBRT (Intensity modulated radiotherapy (IMRT) / Image guided radiotherapy (IGRT) / Stereotactic Body Radiation Therapy (SBRT) / ):
technique: IMRT/IGRT/SBRT The HypoFocal-SBRT study combines ultra-hypofractionated RT / stereotactic body RT (reduction of treatment time) with a focal RT dose escalation on intraprostatic tumor sides by applying state of the art diagnostic imaging and most modern RT concepts.
Radiotherapy (RT) Arm B - IMRT/IGRT (Intensity modulated radiotherapy (IMRT) / Image guided radiotherapy (IGRT) / ):
technique: IMRT/IGRT Moderate hypofractionated RT (MHRT), one option for the curative primary treatment of PCa, which has been proven by several prospective trials and is recommended and carried out worldwide.

Quelle: ClinicalTrials.gov

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