Artificial Intelligence to Personalize Prostate Cancer Treatment (the HypoElect Trial) (HypoElect)

Whole-pelvis Hypofractionated Radiotherapy Combined with Dose-escalation to the Prostate and Androgen Deprivation Therapy in Primary Localized, NCCN and MMAI High-risk Prostate Cancer - a Prospective, Single-arm, Phase II Study

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).

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: High-Dose-Rate Interstitial Brachytherapy (HDR BRT); Drug: Androgen Deprivation Therapy (ADT) - Goserelin; Radiation: radiotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elena Pallari, PhD; Phone Number: 0035725028690; Email: elena.pallari@goc.com.cy
• Study Contact Backup: Name: Kristis Vevis, PhD; Phone Number: 0035725208159; Email: kristis.vevis@goc.com.cy

Study Locations

• Cyprus
  • Limassol, Cyprus, 4108
    • Recruiting
    • German Oncology Center
    • Contact: Elena Pallari, PhD; Phone Number: +35725208690; Email: elena.pallari@goc.com.cy
    • Contact: Kristis Vevis, PhD; Phone Number: +35725208159; Email: kristis.vevis@goc.com.cy
    • Contact: Constantinos Zamboglou, MD
    • Contact: Iosif Strouthos, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single experimental arm; 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

Radiation: High-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.); Drug: Androgen 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; Radiation: radiotherapy; EBRT prostate + elective pelvis (Ultra-hypofractionated): 25 Gy in 5 Gy per fraction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: German Oncology Center, Cyprus
• Investigators: Principal Investigator: Iosif Strouthos, MD, German Medical Institute; Principal Investigator: Constantinos Zamboglou, MD, German Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: prostate cancer; radiotherapy; phase II; multimodal AI
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Goserelin
• Other Study ID Numbers: 2024-PRC-015; U1111-1310-7485 (Other Identifier: World Health Organization Universal Trial Number (UTN))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No