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Prostate CancerPhase 2/3THUNDERNCT06282588

Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers

A Phase 2/3 study testing Darolutamide, Radiotherapy and Zoladex 3.6Mg Implant in people with Prostate Cancer, run by Cancer Research Antwerp at 9 sites in Belgium.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This Investigator-initiated, Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers (THUNDER) study will be conducted in subjects with high-risk localized or locally advanced prostate cancer (PCa). Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Darolutamide, Radiotherapy and Zoladex 3.6Mg Implant
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
493 participants
Where
9 sitesBelgium
Study dates
13 Dec 2023to 31 Dec 2030
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histopathology-proven PCa
  • High-risk locally advanced disease is defined as any of the following factors: PSA > 20 ng/mL OR T-stage 3 or 4 OR Gleason score 8-10 OR cN1.
  • Note: documentation of the clinical T-stage may be obtained from any clinical assessment acceptable for clinical T staging including physical exam (DRE), transrectal ultrasound, CT or MRI. Documentation for the N1 stage can be defined on CT or MRI.
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1.
  • Willingness to undergo a PSMA PET/ CT with or without contrast.
  • Subjects who are PSMA PET/ CT positive for at least one regional or distant (extra-pelvic) lesion at screening (PSMA PET scans will be assessed as described in the study imaging manual), will be eligible to be randomized to either arm of the Phase 3 study. A lesion is considered positive if it has a E-PMSA score of 4 or 5.
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  • Pending confirmation of their Decipher score, subjects who are PSMA PET/ CTnegative for regional or distant lesions at screening (PSMA PET scans will be assessed as described in the study imaging manual), will be eligible for inclusion in either the Phase 3 study (if a high [> 0.85] Decipher score is confirmed) or the non-randomized Phase 2 study (if a low/ intermediate [≤ 0.85] Decipher score is confirmed).
  • Willingness to have their primary tumor sequenced for determination of Decipher score
  • Subjects who have a negative PSMA PET/ CT and a tumor with a low/ intermediate Decipher score (≤ 0.85) will be eligible to enter the non-randomized Phase 2 study.
  • Subjects who have a negative PSMA PET/ CT and a tumor with a high Decipher score (> 0.85) will be eligible to be randomized to either arm of the Phase 3 study.
  • In subjects with positive PSMA PET/ CT, the Decipher score will not determine the treatment allocation.
  • Willingness to undergo SOC RT and long-term ADT (treatment with darolutamide and/ or LHRHA)
  • Subject is able and willing to provide written informed consent, which includes compliance with and ability to undergo all study procedures and attend the scheduled follow-up visit/s per protocol.
  • Subject must be over 18 years of age.
  • Subject able to swallow whole study drug tablets.
  • To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 3 months after the last administration of study treatment. Donation of sperm is not allowed during the treatment phase and for 3 months after the last administration of study treatment.
  • Adequate organ function determined by the following local laboratory values:
  • Adequate bone marrow function: Hemoglobin ≥ 100 g/L, white cell count (WCC) ≥ 4.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelets > 100 x 109/L
  • Adequate renal function: calculated creatinine clearance > 30 mL/min (Cockroft-Gault)
  • Adequate liver function: ALT < 2 x upper limit of normal (ULN) and total bilirubin < 1.5 x ULN, (or if total bilirubin is between 1.5 to 2 x ULN, they must have a normal conjugated bilirubin)
  • Testosterone levels > 50 ng/dL

Who cannot join

  • Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e., bone scan, CT scan, MRI)
  • PCa with predominant non-adenocarcinoma features (sarcomatoid or spindle or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma)
  • Prior pelvic radiotherapy
  • Contraindications for pelvic radiotherapy
  • Contraindications for ADT (treatment with darolutamide and/ or LHRHA)
  • Contraindications or known allergy to PSMA PET/ CT tracers.
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  • Prior local therapy for PCa (e.g., radical prostatectomy, high-intensity focused ultrasound [HIFU], cryotherapy). Subjects with previous transurethral resection of the prostate (TURP) or Millin prostatectomy are eligible for participation
  • Prior systemic therapy for PCa, except for patients with a positive PSMA PET/ CT staging with ADT started no more than 4 weeks prior to randomization.
  • Current use of 5-alpha reductase inhibitor Note: if the alpha reductase inhibitor is stopped ≥ 2 weeks prior to enrollment, the subject is eligible.
  • Current chronic use of opioid analgesics, for ≥3 weeks for oral or ≥7 days for non-oral formulations
  • History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness within ≤1 year prior to enrollment; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  • Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject
  • Major surgery within 21 days prior to enrollment.
  • History of:
  • Loss of consciousness or transient ischemic attack or stroke within 6 months prior to enrollment, or
  • Significant cardiovascular disease within 6 months prior to enrollment: including myocardial infarction, unstable angina, congestive heart failure (New York Heart Association [NYHA] classification Grade 2 or greater), ongoing arrhythmias of Grade > 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0), thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism), coronary artery bypass graft. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of darolutamide, including difficulty swallowing tablets
  • History of another malignancy within 5 years prior to enrollment except for those malignancies treated with curative intent with a predicted risk of relapse of less than 10% including but not limited to non-melanoma carcinoma of the skin; or adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e., Tis, Ta and low grade T1 tumors). All such cases with a history of malignancy within the last 5 years are to be discussed with study team before enrollment. Melanoma in-situ and other adequately treated in-situ neoplasms are not considered malignancies for the purposes of eligibility assessment
  • Concurrent illness, including severe infection that might jeopardize the ability of the subject to undergo the procedures outlined in this protocol with reasonable safety (human immunodeficiency virus [HIV] infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant darolutamide)
  • Subjects who are sexually active with women of childbearing potential and not willing/able to use medically acceptable and highly effective forms of contraception during study treatment and for at least 3 months after the last administration of study treatment. Contraception must include: Additional birth control with low failure rate (less than 1% per year) when used consistently and correctly, e.g., combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone releasing system (IUS), bilateral tubal occlusion, vasectomized partner, true sexual abstinence.

Trial locations and contacts

9 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Piet Ost, MD, PhD contact

003234433759

cancertrials@zas.be

9 sites in 1 country

Belgium9 sites, 9 recruiting

  • AZORG

    Aalst, 9300

    Samuel Bral

    Samuel Bral

    Recruiting

  • AZ Sint-Jan

    Bruges, 8000

    Sabine Meersschout

    Sabine Meersschout

    Recruiting

  • Saint Luc

    Brussels, 1200

    Ad Vandermeulen

    Ad Vandermeulen

    Recruiting

  • UZ Gent

    Ghent, 9000

    Valérie Fonteyne

    Valérie Fonteyne

    Recruiting

  • AZ Groeninge

    Kortrijk, 8500

    Nick Liefhooghe

    Nick Liefhooghe

    Recruiting

  • CHU Liège

    Liège, 4000

    Brieuc Sautois

    Brieuc Sautois

    Recruiting

  • AZ Delta

    Roeselare, 8800

    Lorenzo Staelens

    Benedikt Enge

    Recruiting

  • VITAZ

    Sint-Niklaas, 9100

    Bart De Troyer

    Bart De Troyer

    Recruiting

  • ZAS Sint-Augustinus

    Wilrijk, Antwerp, 2610

    Piet Ost, MD, PhD, cancertrials@zas.be

    Piet Ost

    Recruiting

Other trials in Belgium

About this study

Official title: Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers (THUNDER): A Two-part Phase 2/ 3 Trial

This Investigator-initiated, Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers (THUNDER) study will be conducted in subjects with high-risk localized or locally advanced prostate cancer (PCa). The study contains both a randomized Phase 3 treatment intensification study, as well as a treatment de-intensification non-randomized Phase 2 study. The aim of the THUNDER study is to improve the outcome of high-risk PCa by improved risk stratification. Novel radiotracers and a genomic classifier (Decipher) will be used to guide treatment decisions, instead of standard imaging which is limited by lower sensitivity and specificity.

The hypothesis for the study is that treatment intensification based on a positive PSMA PET/ CT scan or Decipher high score (> 0.85) improves time to new metastases detected on PSMA PET/ CT in high-risk PCa. In patients who are PSMA PET/ CT negative with a low/ intermediate Decipher score (≤ 0.85), it is hypothesized that treatment de-intensification will improve patient quality of life while maintaining a good oncological outcome.

The study will be conducted at multiple centers across Europe. Participation in the study will comprise a screening period, where the screening assessments must be completed before subjects are enrolled and randomized (only for Phase 3 subjects). Eligible, consenting subjects will then undergo treatment according to their assigned study phase and treatment group, to occur over up to 96 weeks (24 months) with a post-treatment follow-up period to monitor safety and efficacy. The study will be closed when 96 events have been registered for the primary endpoint, which is expected to be at 7-8 years from the time of randomization of the first subject.

Read the detailed description

Approximately 360 evaluable patients determined to have high-risk localized or locally advanced PCa, with PSMA positive non-localized disease or a Decipher high score (> 0.6) will be enrolled to the Phase 3 trial. Subjects with PSMA positive non-localized disease for which a Decipher result cannot be obtained, will also be enrolled to the Phase 3 study.

All Phase 3 subjects will be randomly assigned in a 1:1 ratio to receive darolutamide plus Luteinizing hormone releasing hormone (ant)-agonists (LHRHA), or darolutamide matched placebo plus LHRHA, for up to 96 weeks (24 months). All Phase 3 subjects will also receive primary standard of care (SOC) radiation therapy (RT). Subjects in Phase 3 should be commenced on an LHRHA and darolutamide or placebo within 14 days after randomization (unless started earlier) plus SOC RT. Only patients with a PSMA PET-CT showing more than 5 M1 lesions are allowed to receive docetaxel in both arms of the Phase 3 trial. Docetaxel should be started within 4 weeks from randomization. Randomization of Phase 3 subjects will be stratified by 1 versus > 1 high-risk features, N1 versus M1 PSMA positive versus PSMA negative disease, Decipher low/ intermediate versus high versus unknown score and clinical trial site.

Approximately 133 evaluable patients determined to have localized PCa by PSMA PET/ CT (PSMA negative) with a low/ intermediate Decipher test score (≤ 0.85) will enter the non-randomized, Phase 2, single treatment arm, de-intensification study. Subjects with localized PCa by PSMA PET/ CT who return a high Decipher score (> 0.85) will be enrolled and randomized into the Phase 3 study. Subjects with localized PCa by PSMA PET/ CT for which a Decipher result cannot be obtained, will be deemed ineligible for study participation.

All Phase 2 study subjects will receive darolutamide for the study duration for up to 96 weeks (24 months) and primary SOC RT.

Conditions
Prostate Cancer
Being tested
Darolutamide, Darolutamide matched placebo, Radiotherapy, Zoladex 3.6Mg Implant, Zoladex LA
Keywords
High-risk, PSMA PET/CT scan, Decipher
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarolutamideDrug

    Also called Nubeqa, BAY1841788

    2x300 mg tablets twice daily, for up to 96 weeks

  • Darolutamide matched placeboDrug

    Also called BAY1841788 matched placebo

    2x300 mg tablets twice daily, for up to 96 weeks

  • RadiotherapyRadiation

    Preferred regimens: 60 to 62 Gy delivered in 20 fractions of 3.0 to 3.1Gy per fraction; 36.25 Gy delivered in 5 fractions of 7.25 Gy per fraction, 2-3 fractions per week

  • Zoladex 3.6Mg ImplantDrug

    Also called Goserelin acetate 3.6 mg

    3.6 mg, subcutaneous use

  • Zoladex LADrug

    Also called Goserelin acetate 10.8 mg

    10.8 mg, subcutaneous use

  • Decapeptyl sustained release 22.5 mgDrug

    Also called Triptorelin 11.25 mg

    22.5 mg, intramusculair injection

  • Decapeptyl sustained release 11.25 mgDrug

    Also called Triptorelin 11.25 mg

    11.25 mg, intramusculair injection

  • Depo-Eligard 45 mgDrug

    Also called Leuprorelin acetate 45 mg

    45 mg, subcutaneous use

  • Depo-Eligard 22.5 mgDrug

    Also called Leuprorelin acetate 22.5 mg

    22.5 mg, subcutaneous use

  • Depo-Eligard 7.5 mgDrug

    Also called Leuprorelin acetate 7.5 mg

    7.5 mg, subcutaneous use

  • Firmagon 120 MG InjectionDrug

    Also called Degarelix 40 mg

    120 mg, subcutaneous use

  • Firmagon 80 MG InjectionDrug

    Also called Degarelix 20 mg

    80 mg, subcutaneous use

  • DocetaxelDrug

    Also called Taxotere

    75 mg per square m, IV infusion

Study groups in NCT06282588
Study groupRoleWhat they receive
Phase 2 Open LabelExperimentalDarolutamide for up to 96 weeks (24 months) and primary SOC RT
Receives: Drug: Darolutamide; Radiation: Radiotherapy
Phase 3 Blinded ExperimentalExperimentalDarolutamide + LHRHA for up to 96 weeks (24 months) and primary SOC RT
Receives: Drug: Darolutamide; Radiation: Radiotherapy; Drug: Zoladex 3.6Mg Implant; Drug: Zoladex LA; Drug: Decapeptyl sustained release 22.5 mg; Drug: Decapeptyl sustained release 11.25 mg; Drug: Depo-Eligard 45 mg; Drug: Depo-Eligard 22.5 mg; Drug: Depo-Eligard 7.5 mg; Drug: Firmagon 120 MG Injection; Drug: Firmagon 80 MG Injection; Drug: Docetaxel
Phase 3 Blinded ComparatorPlacebo comparatorDarolutamide matched placebo + LHRHA for up to 96 weeks (24 months) and primary SOC RT
Receives: Drug: Darolutamide matched placebo; Radiation: Radiotherapy; Drug: Zoladex 3.6Mg Implant; Drug: Zoladex LA; Drug: Decapeptyl sustained release 22.5 mg; Drug: Decapeptyl sustained release 11.25 mg; Drug: Depo-Eligard 45 mg; Drug: Depo-Eligard 22.5 mg; Drug: Depo-Eligard 7.5 mg; Drug: Firmagon 120 MG Injection; Drug: Firmagon 80 MG Injection; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 3: PSMA PET metastasis free survival (ppMFS)

    Improvement in PSMA PET metastasis free survival (ppMFS)

    Measured: Time from randomization to the date of at least 1 new PSMA-PET positive distant lesion as compared to baseline or date of death from any cause, assessed up to 42 months

  2. Phase 2: quality of life (sexual subdomain)

    EPIC mean changes in sexual subdomain scores over time will be compared, both for change from baseline and absolute scores

    Measured: At 12 months

  3. Phase 2: quality of life (hormonal subdomain)

    EPIC mean changes in hormonal subdomain scores over time will be compared, both for change from baseline and absolute scores

    Measured: At 12 months

Secondary outcomes (5)

  1. Overall survival

    Overall survival

    Measured: Time interval between randomization and time of death, assessed up to 42 months

  2. Prostate-cancer specific survival

    Prostate-cancer specific survival

    Measured: Time interval between randomization and prostate cancer death, assessed up to 42 months

  3. Biochemical progression-free survival

    Increase in PSA of >2 ng/ml above the nadir PSA level

    Measured: Measured from the date of randomization to the date event, or death or censored at the last known follow-up date, assessed up to 42 months

  4. Time to next systemic therapy

    Time to next systemic therapy

    Measured: Measured from date of randomization to time of death, or censored at the last known follow-up date, assessed up to 42 months

  5. Frequency and severity of adverse events

    Frequency and severity of adverse events

    Measured: From signing ICF until 30 days after the last dose of study treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2024
  2. Study start13 Dec 2023
  3. Primary completion31 Jul 2030 (estimated)
  4. Study completion31 Dec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Phase 2: non randomised, 1 treatment arm, open label Phase 3: randomized 1:1 between two treatment arms, blinded
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
493 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06282588
Sponsor's protocol ID
CTO21042GZA
Acronym
THUNDER
Status last verified
Mar 2026
First submitted
19 Jan 2024
Last updated
19 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kleiburg F, Dirix P, Fonteyne V, Bral S, De Troyer B, Sautois B, Lamande M, Liefhooghe N, Grisay G, Meersschout S, Vandermeulen A, Jullian N, Staelens L, Poelaert F, Strijbos M, Verschueren J, Goffin K, Withofs N, Ost P. Stage Migration on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Comparison to Conventional Imaging in Patients with High-risk Prostate Cancer Referred for Radiation Therapy: Results from the Phase 2/3 THUNDER Trial. Eur Urol Oncol. 2025 Oct;8(5):1333-1339. doi: 10.1016/j.euo.2025.08.005. Epub 2025 Sep 25.

    PubMed 40998687

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Darolutamide, Radiotherapy and Zoladex 3.6Mg Implant in people with Prostate Cancer, run by Cancer Research Antwerp at 9 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Piet Ost, MD, PhD (003234433759, cancertrials@zas.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 3: PSMA PET metastasis free survival (ppMFS) (time frame: Time from randomization to the date of at least 1 new PSMA-PET positive distant lesion as compared to baseline or date of death from any cause, assessed up to 42 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06282588, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.

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