Artificial Intelligence Driven Personalisation of Radiotherapy and Concomitant Androgen Deprivation Therapy for Prostate Cancer Patients (the HypoPro Trial) (HypoPro)

January 8, 2025 updated by: German Oncology Center, Cyprus

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In Cyprus approximately 800 men are newly diagnosed with PCa every year. Prostate cancer caused 6.1 million disability-adjusted life-years (DALYs) globally in 2016. The socio-economic burden is high since PCa-related life-time costs are approximately 40,000 per patient with early stage disease at initial diagnosis.

This is a prospective, single-center phase II trial. Patient participants will receive treatment for prostate +-seminal vesicles base high-dose-rate brachytherapy (HDR BT) with 15 Gray units (Gy) with minimal dose covering 90% of the prostate (D90) / 1 fraction followed by stereotactic body radiation therapy (SBRT) with 25 Gy in 5 Gy / fraction (daily); of the prostate +- seminal vesicles. Concomittant/adjuvant admission of 12 months ADT.

First: 1 fraction HDR BT including fiducial placement Second: 14 ±2 days gap Third: 5 fractions of SBRT within 5 consecutive weekdays For the HypoPro patients, we expect no significant differences in disease-free survival (DFS) rates compared to the FLAME trial (2) which one arm treated the patients with moderately-hypofractionated RT to the prostate plus dose escalation to the intraprostatic tumor plus 18-24 months of ADT. Secondary endpoints like metastatic free survival, prostate cancer survival and overall survival will depict the oncologic efficacy in this patient cohort. Thus, the results of this study might be used as the basis for a randomized-controlled trial comparing this dose escalated radiotherapy plus shortened ADT duration with the standard of care (no dose escalated RT, ADT for 2-3 years) in this highly selected treatment group: NCCN high-risk, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) cN0/cM0 and MMAI low/intermediate-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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Cyprus
      • Limassol, Cyprus, 4108
        • Recruiting
        • German Oncology Center
        • Contact:
        • Contact:
        • Contact:
          • Constantinos Zamboglou, MD
        • Contact:
          • Iosif Strouthos, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single experimental arm
Prostate +/-seminal vesicles base HDR BT with 15 Gy (D90) / 1 fraction followed by SBRT with 25 Gy in 5 Gy / fraction (daily); of the prostate +- seminal vesicles. Concomittant/adjuvant admission of 12 months ADT.
Drug: Androgen deprivation therapy (ADT)
  • Goserelin: AstraZeneca, 10.8mg injection
  • ADT will be applied for 12 months in total
  • ADT must be given concurrently and adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival 5 years after treatment
Time Frame: Five years
Disease recurrence is defined as PSA failure according to Phoenix, new lesions on PSMA PET and/or MRI imaging or the beginning of any salvage therapy.
Five years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to local or regional failure, after end of RT
Time Frame: Two and five years after RT
Local or regional recurrences have to be confirmed by PSMA-PET or mpMR imaging. For the diagnosis of local failure, verification via biopsy is warranted
Two and five years after RT
Metastatic free survival (MFS) after end of RT
Time Frame: Two and five years after RT
MFS is defined as survival time in months from beginning of RT until detection of any new lesion confirmed as metastasis by PSMA-PET/CT or mpMR imaging or death.
Two and five years after RT
Overall survival (OS)
Time Frame: Assessment at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT
OS will be measured from the last day of RT to the date of death whatever the cause of death is. Patients who are alive are censored at the date of the most recent follow-up examination. The cause of death of each patient dying during the study will be recorded and reported.
Assessment at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT
Prostate cancer specific survival (PCSS)
Time Frame: Assessment at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT
PCSS is defined from the last day of RT until death as most reasonable consequence of progressive prostate cancer, judged by the investigator.
Assessment at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT
Biochemical failure
Time Frame: Two and five years after RT
Time to biochemical failure after end of RT (phoenix definition)
Two and five years after RT
Quality of Life (QoL)
Time Frame: 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)
Patient-reported outcome measures (PROMs) EPIC-26: the Expanded Prostate Cancer Index-Short form) with score: 0-100
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)
Quality of Life (QoL)
Time Frame: 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)
Patient-reported outcome measures (PROMs) IIEF-5: The International Index of Erectile Function with score: 0-5
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)
Genitourinary (GU) acute toxicities
Time Frame: During, at 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)
During, at 1 and 3 months after RT
GU acute toxicities
Time Frame: During, at 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)
During, at 1 and 3 months after RT
GU chronic toxicities
Time Frame: During, at 1 and 3 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)
During, at 1 and 3 months after RT
GU chronic toxicities
Time Frame: during, 1 and 3 months after RT
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)
during, 1 and 3 months after RT
Gastrointestinal (GI) acute toxicities
Time Frame: 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)
During, 1 and 3 months after RT
GI acute toxicities
Time Frame: During, at 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)
During, at 1 and 3 months after RT
GI chronic toxicities
Time Frame: Assessment at 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)
Assessment at 6, 9, 12, 18, and 24 months after RT
GI chronic toxicities
Time Frame: Assessment at 6, 9, 12, 18, and 24 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)
Assessment at 6, 9, 12, 18, and 24 months after RT
Testosterone recovery
Time Frame: 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 a 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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German Oncology Center, Cyprus

Collaborators

Artera

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Estimated)

October 31, 2026

Study Completion (Estimated)

October 31, 2027

Study Registration Dates

First Submitted

January 3, 2025

First Submitted That Met QC Criteria

January 8, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 8, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-PRC-062
  • 2024-510707-11-00 (Ctis)
  • U1111-1309-9298 (Other Identifier: World Health Organization 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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