Prostate-only, Dose-escalated Radiotherapy Plus Concomitant Androgen Deprivation Therapy in Primary Localized, NCCN High Risk and MMAI Classifier Low or Intermediate-risk Prostate Cancer - a Prospective, Single-arm, Phase II Study
Trial ID: NCT06772441
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE2
Start date: 2024-11-01
Completion date: 2027-10-31
Sponsor: German Oncology Center, Cyprus
Collaborators: Artera
Conditions: Prostate Cancer
Interventions: Androgen deprivation therapy (ADT)
Locations: German Oncology Center
Countries: Cyprus
Enrollment: 30
Age range: 18 Years - None
Sex: MALE

Summary:
The aim of this prospective, single-arm phase II study is the individualization of both radiotherapy (RT) and androgen deprivation therapy (ADT) duration for patients with high-risk localized prostate cancer (PCa) according to the National Comprehensive Cancer Network (NCCN) based on multimodal artificial intelligence (MMAI) classification. All patients will receive (i) a dose escalation to the prostate via HDR brachytherapy (boost), (ii) twelve months of ADT and (iii) extremely hypofractionated RT to the prostate (5 fractions).

This way, patients in the HypoPro trial will receive a prostate-only dose escalation and benefit from shortening of the ADT compared with current guideline recommendations.

Eligibility criteria:
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 PCa (in PSMA-PET imaging and multiparametric magnetic resonance imaging (mpMRI)
3. High-risk according to NCCNv4.2023 criteria (cT3a or Grade group 4-5 or PSA \> 20 ng/ml)
4. Signed written informed consent for this study
5. Age \>18 years
6. Previously conducted PSMA-PET/CT, mpMRI or PSMA-PET/MR
7. MMAI low-/intermediate-risk
8. ECOG Performance score 0 or 1
9. IPSS Score ≤15
10. Prostate biopsy core with the highest ISUP grade available

Exclusion Criteria:

1. Prior radiotherapy to the prostate or pelvis
2. Prior radical prostatectomy
3. Prior focal therapy approaches to the prostate
4. Evidence of pelvic nodal disease (cN+) in mpMRI and/or PSMA-PET/CT
5. Evidence of distant metastatic disease (cM+) in mpMRI and/or PSMA-PET/CT
6. Time gap between the beginning of any systemic therapy, ADT and conduction of PSMA-PET scans is \>2 months
7. Evidence of cT4 disease in mpMRI and/or PSMA-PET/CT
8. PSA \>50 ng/ml prior to starting of systemic therapy
9. Expected patient survival \<5 years
10. Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artifacts
11. Contraindication to undergo a MRI scan
12. Contraindication to undergo HDR brachytherapy (brachytherapy not feasible due to large prostate volume, prostate anatomy, tumor in distant seminal vesicles and/or unfit for anaesthesia)
13. Contraindication to Goserelin
14. Prostate surgery (TURP or HOLEP) with a significant tissue cavity or prostate surgery (TURP or HOLEP) within the last 6 months prior to randomization
15. Medical conditions likely to make radiotherapy inadvisable e.g. acute inflammatory bowel disease, hemiplegia or paraplegia
16. 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
17. Any other contraindication to external beam radiotherapy (EBRT) to the pelvis
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 (e.g. mental condition)

Outcomes:
Disease-free survival 5 years after treatment