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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1310-7485 | Other Identifier | World Health Organization Universal Trial Number (UTN) |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single experimental arm | Experimental | RT prostate (HDR brachytherapy): 15 Gy (D90) in 1 fraction HDR RT prostate EBRT elective pelvis (Ultra-hypofractionated RT - UHF): 25 Gy in 5 Gy per fraction Technique: IMRT/IGRT/HDR brachytherapy Duration: 6 fractions, 3 weeks Androgen deprivation therapy (ADT) - Goserelin: all patients receive ADT; luteinising-hormone-releasing hormone agonists or antagonists for 24 months Follow-up (FU) per patient: minimum FU time is 5 years (60 months), the study ends when the last enrolled patients reaches 60 months of FU time Further FU: by the end of this clinical trial it will be decided whether further FU is necessary, amendment to this clinical trial protocol will be done in appropriate time |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Androgen Deprivation Therapy (ADT) - Goserelin | Drug | The patients under ADT and the patients who will receive the ADT during the study will be included in the trial.
|
| Measure | Description | Time Frame |
|---|---|---|
| cumulative GU toxicity | Primary endpoint is cumulative GU toxicity according to RTOG grading after minimum FU time of two years. | two years |
| Measure | Description | Time Frame |
|---|---|---|
| Time to local or regional failure | 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. | two and five years after RT |
| MMAI classifier |
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Inclusion Criteria:
Exclusion Criteria:
Males with prostate cancer. Eligibility is based on histologically confirmed adenocarcinoma of the prostate
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Elena Pallari, PhD | Contact | 0035725028690 | elena.pallari@goc.com.cy | |
| Kristis Vevis, PhD | Contact | 0035725208159 | kristis.vevis@goc.com.cy |
| Name | Affiliation | Role |
|---|---|---|
| Iosif Strouthos, MD | German Medical Institute | Principal Investigator |
| Constantinos Zamboglou, MD | German Medical Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| German Oncology Center | Recruiting | Limassol | 4108 | Cyprus |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40645505 | Derived | Zamboglou C, Doncker W, Christoforou AT, Arcangeli S, Berlin A, Blanchard P, Bauman G, Campi R, Castro E, Choudhury A, Pra AD, Draulans C, Desai N, Ferentinos K, Francolini G, Gillessen S, Grosu AL, Rivas JG, Hoelscher T, Hruby G, Jereczek-Fossa BA, Kamran S, Kasivisvanathan V, Kishan AU, Kounnis V, Loblaw A, Martin J, Mastroleo F, Merseburger AS, Miszczyk M, Mohamad O, Ost P, Papatsoris A, Peeken JC, Sanguedolce F, Sargos P, Schmidt-Hegemann N, Seibert TM, Shelan M, Siva S, Soeterik TFW, Spratt DE, Stenzl A, Strouthos I, Sutera P, Supiot S, Tilki D, Tran PT, Tree AC, Tward J, Urun Y, Vapiwala N, Waddle MR, Wegener E, Zilli T, Murthy V, Thieme AH, Spohn S. oDigital pathology biomarkers for guiding radiotherapy-based treatment concepts in prostate cancer - a systematic review and expert consensus. Radiother Oncol. 2025 Sep;210:111039. doi: 10.1016/j.radonc.2025.111039. Epub 2025 Jul 9. |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000726 | Androgen Antagonists |
| D017273 | Goserelin |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
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| High-Dose-Rate Interstitial Brachytherapy (HDR BRT) | Radiation | 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.) |
|
| radiotherapy | Radiation | EBRT prostate + elective pelvis (Ultra-hypofractionated): 25 Gy in 5 Gy per fraction |
|
Prognostic influence of MMAI classifier for outcome; the ArteraAI Prostate Test score (ranging from 0.0 to 1.0) |
| 5-year and 10-year risk prediction of distant metastasis and 10-year risk of prostate-specific mortality. |
| Testosterone | Testosterone recovery is to be done through blood test | 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 |
| Metastatic free survival (MFS) | MFS after end of RT, (all metastases have to be confirmed by PSMA-PET/CT or mpMR imaging) | two and five years after RT |
| Overall Survival (OS) | OS after end of RT | 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT |
| Prostate cancer specific survival (PCSS) | PCSS after end of RT | 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT |
| Biochemical failure | Time to biochemical failure after end of RT (phoenix definition) | two and five years after RT |
| Quality of Life (QoL) | Patient-reported outcome measures (PROMs) EPIC-26: the Expanded Prostate Cancer Index-Short form) with score: 0-100 | 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) |
| QoL | Patient-reported outcome measures (PROMs) IIEF-5: The International Index of Erectile Function with score: 0-5 | 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) |
| QoL | Patient-reported outcome measures (PROMs) IPSS: International prostate symptom score with score 0-5 | 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) |
| Genitourinary (GU) acute toxicities | 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) | during, 1 and 3 months after RT |
| GU acute toxicities | 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) | during, 1 and 3 months after RT |
| GU chronic toxicities | 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) | 6, 9, 12, 18 and 24 months after RT |
| GU chronic toxicities | Cumulative chronic 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) | 6, 9, 12, 18 and 24 months after RT |
| Gastrointestinal (GI) acute toxicities | 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) | during, 1 and 3 months after RT |
| GI acute toxicities | 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) | during, 1 and 3 months after RT |
| GI chronic toxicities | 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) | 6, 9, 12, 18 and 24 months after RT |
| GI chronic toxicities | Cumulative chronic 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) | 6, 9, 12, 18 and 24 months after RT |
| Dose contrainsts | 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) | during, 1 and 3 months after RT |
| Dose contrainsts | Feasibility to dose constraints for pelvic lymph nodes irradiation Pelvic EBRT PTV, Constraint, Vol cc or % PTV P/SV, V95 ≥, 95 PTV LV, V95 ≥, 95 Dmax LV, max < 107 Dmax SIB, max < 107 OAR: Rectum Constraint, Vol cc or % V18Gy < (%), 50 V20Gy < (%), 30 D1cc ≤ (Gy), 26 OAR: Sigmoid Constraint, Vol cc or % V18Gy < (%), 50 V20Gy < (%), 30 D1cc ≤ (Gy), 26 OAR: Bladder Constraint, Vol cc or % V18Gy < (%), 50 V20Gy < (%), 30 D1cc ≤ (Gy), 26 OAR: Femoral Head L Constraint, Vol cc or % D10cc ≤ (Gy), 25 OAR: Femoral Head R Constraint, Vol cc or % D10cc ≤ (Gy), 25 OAR: Bowel Cavity (including sigmoid) Constraint, Vol cc or % V25Gy < (cc), 40 D1cc ≤ (Gy), 26 OAR: Penile bulb Constraint, Vol cc or % Mean < (Gy), 20 | during, 1 and 3 months after RT |
| Dose contrainsts | Adherence to dose constraints for pelvic lymph nodes irradiation Interruptions of RT in days along with reasons | during, 1 and 3 months after RT |
| Dose contrainsts | Adherence to dose constraints for pelvic lymph nodes irradiation Treatment not finished due to set-up problems (YES/NO) and reason | during, 1 and 3 months after RT |
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D020164 | Chemical Actions and Uses |
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D013812 | Therapeutics |