Prostate Cancer
Conditions
Keywords
prostate cancer, multimodal AI, radiotherapy, phase II
Brief summary
A prospective, single-arm phase II study is the individualization of RT for patients with high-risk localized PCa based on multimodal artificial intelligence (MMAI). All patients will receive the current standard of care: (i) a dose escalation to the prostate via HDR brachytherapy, (ii) two years of ADT and (iii) whole-pelvis UHF-RT (5 fractions).
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. For primary high-risk localized PCa patients, NCCNv4.2023 guidelines recommend normo- or hypofractionated RT to the prostate ± the elective pelvic lymphatics and systemic treatment in terms of ADT. Although the standard of care, the benefit of this therapy regimen is controversially discussed: the benefit of (i) an RT dose escalation using brachytherapy (2) or focal dose escalated RT(3) or (ii) an elective RT of the pelvic lymph nodes (1) is not finally proven yet. In parallel, first studies proposed a reduction in treatment fractions in terms of ultra-hypofractionated RT (UHF-RT) (4). The aim of this prospective, single-arm phase II study is the individualization of RT for patients with high-risk localized PCa based on MMAI. All patients will receive the current standard of care: (i) a dose escalation to the prostate via HDR brachytherapy, (ii) two years of ADT and (iii) whole-pelvis UHF-RT (5 fractions). For the HypoElect patients we expect no significant differences in toxicity rates compared to the randomized controlled POP-RT trial (1) which treated the patients with moderately-hypofractionated RT to the prostate and the elective pelvic lymph nodes in parallel to 24 months of ADT. Secondary endpoints like relapse free survival, metastatic free survival, prostate cancer survival and overall survival will depict the oncologic efficacy in this patient cohort. Thus, the safety and oncologic outcome results of this study might be the first in this highly selected treatment group: NCCN high-risk, PSMA PET cN0/cM0 and MMAI high-risk. 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 to predict the treatment outcome.
Interventions
DRUGAndrogen Deprivation Therapy (ADT) - Goserelin
The patients under ADT and the patients who will receive the ADT during the study will be included in the trial. * ADT will be applied for 24 months in total * ADT must be given concurrently and adjuvant
RADIATIONHigh-Dose-Rate Interstitial Brachytherapy (HDR BRT)
HDR BRT Procedure will be performed using transperineal catheter implantation under transrectal US-guidance performed under anesthesia, spinal or general with patient in high lithotomy position.)
RADIATIONradiotherapy
EBRT prostate + elective pelvis (Ultra-hypofractionated): 25 Gy in 5 Gy per fraction
Sponsors
German Oncology Center, Cyprus
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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) * Primary PCa (in PSMA-PET imaging and multiparametric magnetic resonance imaging (mpMRI) * High- or very high-risk according to NCCNv1.2023 criteria * Signed written informed consent for this study * Age \>18 years * Previously conducted PSMA-PET/CT, mpMRI or PSMA-PET/MR * MMAI high-risk * ECOG Performance score 0 or 1 * IPSS Score ≤15
Exclusion criteria
* Prior radiotherapy to the prostate or pelvis * Prior radical prostatectomy * Prior focal therapy approaches to the prostate * Evidence of pelvic nodal disease (cN+) in mpMRI and/or PSMA-PET/CT * Evidence of distant metastatic disease (cM+) in mpMRI and/or PSMA-PET/CT * Time gap between the beginning of any systemic therapyADT and conduction of PSMA-PET scans is \>2 months * Evidence of cT4 disease in mpMRI and/or PSMA-PET/CT * PSA \>50 ng/ml prior to starting of systemic therapy * Expected patient survival \<5 years * Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artifacts * Contraindication to undergo a MRI scan * Contraindication to undergo HDR brachytherapy (brachytherapy not feasible due to large prostate volume, prostate anatomy, tumor in distant seminal vesicles and/or unfit for anesthesia) * Prostate surgery (TURP or HOLEP) with a significant tissue cavity or prostate surgery (TURP or HOLEP) within the last 6 months prior to randomization * Medical conditions likely to make radiotherapy inadvisable e.g. acute inflammatory bowel disease, hemiplegia or paraplegia * 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 * Any other contraindication to external beam radiotherapy (EBRT) to the pelvis * Participation in any other interventional clinical trial within the last 30 days before the start of this trial * Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed * Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial * Known or persistent abuse of medication, drugs or alcohol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| cumulative GU toxicity | two years | Primary endpoint is cumulative GU toxicity according to RTOG grading after minimum FU time of two years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to local or regional failure | two and five years after RT | Time to local or regional failure; after end of RT. Local or regional recurrences have to be confirmed by PSMA-PET or mpMR imaging. For the diagnosis of local failure a verification via biopsy is warranted. |
| MMAI classifier | 5-year and 10-year risk prediction of distant metastasis and 10-year risk of prostate-specific mortality. | Prognostic influence of MMAI classifier for outcome; the ArteraAI Prostate Test score (ranging from 0.0 to 1.0) |
| Testosterone | assessment at 6,9,12,18 and 24 months after randomization (± 14 days for each visit) and at 30, 36, 42, 48, 54, 60 months after Ultra-hypofractionated RT - UHF (± 1 month | Testosterone recovery is to be done through blood test |
| Metastatic free survival (MFS) | two and five years after RT | MFS after end of RT, (all metastases have to be confirmed by PSMA-PET/CT or mpMR imaging) |
| Overall Survival (OS) | 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT | OS after end of RT |
| Prostate cancer specific survival (PCSS) | 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT | PCSS after end of RT |
| Biochemical failure | two and five years after RT | Time to biochemical failure after end of RT (phoenix definition) |
| Quality of Life (QoL) | Assessments at 6, 9,12, 18, and 24 months after randomization (± 14 days for each visit) and at 30, 36, 42, 48, 54, 60 months after Ultra-hypofractionated RT - UHF (± 1 month) | Patient-reported outcome measures (PROMs) EPIC-26: the Expanded Prostate Cancer Index-Short form) with score: 0-100 |
| QoL | Assessments at 6, 9,12, 18, and 24 months after randomization (± 14 days for each visit) and at 30, 36, 42, 48, 54, 60 months after Ultra-hypofractionated RT - UHF (± 1 month) | Patient-reported outcome measures (PROMs) IIEF-5: The International Index of Erectile Function with score: 0-5 |
| Genitourinary (GU) acute toxicities | during, 1 and 3 months after RT | Cumulative acute GU toxicities using the RTOG grading system (Radiation Therapy Oncology Group; with grade: 0-5, where 0 implies no toxicity and 5 implies a side effect related to death) |
| GU acute toxicities | during, 1 and 3 months after RT | Cumulative acute GU toxicities using the CTCAE v5.0 criteria (the Common Terminology Criteria for Adverse Events criteria; with grade: 1-5 where 1 means asymptomatic or mild symptoms and 5 means death related to adverse event) |
| GU chronic toxicities | 6, 9, 12, 18 and 24 months after RT | Cumulative chronic GU toxicities using the RTOG grading system (Radiation Therapy Oncology Group; with grade: 0-5, where 0 implies no toxicity and 5 implies a side effect related to death) |
| Gastrointestinal (GI) acute toxicities | during, 1 and 3 months after RT | Cumulative acute GI toxicities using the RTOG grading system (Radiation Therapy Oncology Group; with grade: 0-5, where 0 implies no toxicity and 5 implies a side effect related to death) |
| GI acute toxicities | during, 1 and 3 months after RT | Cumulative acute GU toxicities using the CTCAE v5.0 criteria (the Common Terminology Criteria for Adverse Events criteria; with grade: 1-5 where 1 means asymptomatic or mild symptoms and 5 means death related to adverse event) |
| GI chronic toxicities | 6, 9, 12, 18 and 24 months after RT | Cumulative chronic GU toxicities using the RTOG grading system (Radiation Therapy Oncology Group; with grade: 0-5, where 0 implies no toxicity and 5 implies a side effect related to death) |
| Dose contrainsts | during, 1 and 3 months after RT | Feasibility to dose constraints for pelvic lymph nodes irradiation HDR-BT Prostate CTV=PTV Reference dose DR: 15 Gy (100 %) D90 ≥ 100 % V100 ≥ 95 % V150 ≤ 30 % Rectum (OAR) D2cc ≤ 75Gy EQD2(1.5) D1cc ≤ 70% Urethra (OAR) D0.1cc ≤ 115% D10 ≤ 110% D30 ≤ 105Gy EQD2(1.5) |
Countries
Cyprus
Contacts
CONTACTElena Pallari, PhD
CONTACTKristis Vevis, PhD
PRINCIPAL_INVESTIGATORIosif Strouthos, MD
German Medical Institute
PRINCIPAL_INVESTIGATORConstantinos Zamboglou, MD
German Medical Institute
Outcome results
None listed