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

NCT ID: NCT06772441

Last Updated: 2025-01-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2027-10-31

Brief 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.

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Androgen deprivation therapy (ADT)

Intervention Type: DRUG

• Goserelin: AstraZeneca, 10.8mg injection
• ADT will be applied for 12 months in total
• ADT must be given concurrently and adjuvant

Interventions

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

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Artera

UNKNOWN

Sponsor Role: collaborator

German Oncology Center, Cyprus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

German Oncology Center

Limassol, , Cyprus

Site Status: RECRUITING

Countries

Cyprus

Central Contacts

Elena Pallari, PhD

Role: CONTACT

elena.pallari@goc.com.cy

+357 25028690

Kristis Vevis, PhD

Role: CONTACT

kristis.vevis@goc.com.cy

+357 25208159

Facility Contacts

Elena Pallari, PhD

Role: primary

elena.pallari@goc.com.cy

+357 25208690

Kristis Vevis, PhD

Role: backup

kristis.vevis@goc.com.cy

+357 25208159

Constantinos Zamboglou, MD

Role: backup

Iosif Strouthos, MD

Role: backup

References

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Reference Type: BACKGROUND

PMID: 34588146 (View on PubMed)

van As N, Griffin C, Tree A, Patel J, Ostler P, van der Voet H, Loblaw A, Chu W, Ford D, Tolan S, Jain S, Camilleri P, Kancherla K, Frew J, Chan A, Naismith O, Armstrong J, Staffurth J, Martin A, Dayes I, Wells P, Price D, Williamson E, Pugh J, Manning G, Brown S, Burnett S, Hall E. Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer. N Engl J Med. 2024 Oct 17;391(15):1413-1425. doi: 10.1056/NEJMoa2403365.

Reference Type: BACKGROUND

PMID: 39413377 (View on PubMed)

Spratt DE, Tang S, Sun Y, Huang HC, Chen E, Mohamad O, Armstrong AJ, Tward JD, Nguyen PL, Lang JM, Zhang J, Mitani A, Simko JP, DeVries S, van der Wal D, Pinckaers H, Monson JM, Campbell HA, Wallace J, Ferguson MJ, Bahary JP, Schaeffer EM, Sandler HM, Tran PT, Rodgers JP, Esteva A, Yamashita R, Feng FY. Artificial Intelligence Predictive Model for Hormone Therapy Use in Prostate Cancer. NEJM Evid. 2023 Aug;2(8):EVIDoa2300023. doi: 10.1056/EVIDoa2300023. Epub 2023 Jun 29.

Reference Type: BACKGROUND

PMID: 38320143 (View on PubMed)

Esteva A, Feng J, van der Wal D, Huang SC, Simko JP, DeVries S, Chen E, Schaeffer EM, Morgan TM, Sun Y, Ghorbani A, Naik N, Nathawani D, Socher R, Michalski JM, Roach M 3rd, Pisansky TM, Monson JM, Naz F, Wallace J, Ferguson MJ, Bahary JP, Zou J, Lungren M, Yeung S, Ross AE; NRG Prostate Cancer AI Consortium; Sandler HM, Tran PT, Spratt DE, Pugh S, Feng FY, Mohamad O. Author Correction: Prostate cancer therapy personalization via multi-modal deep learning on randomized phase III clinical trials. NPJ Digit Med. 2023 Feb 22;6(1):27. doi: 10.1038/s41746-023-00769-z. No abstract available.

Reference Type: BACKGROUND

PMID: 36813827 (View on PubMed)

Kerkmeijer LGW, Groen VH, Pos FJ, Haustermans K, Monninkhof EM, Smeenk RJ, Kunze-Busch M, de Boer JCJ, van der Voort van Zijp J, van Vulpen M, Draulans C, van den Bergh L, Isebaert S, van der Heide UA. Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):787-796. doi: 10.1200/JCO.20.02873. Epub 2021 Jan 20.

Reference Type: BACKGROUND

PMID: 33471548 (View on PubMed)

Other Identifiers

2024-510707-11-00

Identifier Type: CTIS

Identifier Source: secondary_id

U1111-1309-9298

Identifier Type: OTHER

Identifier Source: secondary_id

2024-PRC-062

Identifier Type: -

Identifier Source: org_study_id