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

ConditionProstate Cancer
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexMale
Age18+
SponsorCancer Research Antwerp

About this 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

An Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1.

Willingness to undergo a PSMA PET/ CT with or without contrast.

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Darolutamide

    Drug

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

  • Darolutamide matched placebo

    Drug

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

  • Radiotherapy

    Radiation

    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 Implant

    Drug

    3.6 mg, subcutaneous use

  • Zoladex LA

    Drug

    10.8 mg, subcutaneous use

  • Decapeptyl sustained release 22.5 mg

    Drug

    22.5 mg, intramusculair injection

  • Decapeptyl sustained release 11.25 mg

    Drug

    11.25 mg, intramusculair injection

  • Depo-Eligard 45 mg

    Drug

    45 mg, subcutaneous use

  • Depo-Eligard 22.5 mg

    Drug

    22.5 mg, subcutaneous use

  • Depo-Eligard 7.5 mg

    Drug

    7.5 mg, subcutaneous use

  • Firmagon 120 MG Injection

    Drug

    120 mg, subcutaneous use

  • Firmagon 80 MG Injection

    Drug

    80 mg, subcutaneous use

  • Docetaxel

    Drug

    75 mg per square m, IV infusion

Treatment groups

493 Participants
are divided into 3 treatment groups
Group A: Phase 2 Open LabelExperimental treatment 2 interventions
Group B: Phase 3 Blinded ExperimentalExperimental treatment 12 interventions
Group C: Phase 3 Blinded ComparatorPlacebo comparator 12 interventions

Trial outcomes

Primary outcomes

1

Phase 3: PSMA PET metastasis free survival (ppMFS)

Improvement in 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
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

Time frame
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

Time frame
At 12 months

Secondary outcomes

1

Overall survival

Overall survival

Time frame
Time interval between randomization and time of death, assessed up to 42 months
2

Prostate-cancer specific survival

Prostate-cancer specific survival

Time frame
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

Time frame
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

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Cancer Research Antwerp

Lead sponsor

Bayer

Collaborator

Veracyte, Inc.

Collaborator

Source ClinicalTrials.gov
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