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

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). 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.

Conditions

• Prostate Cancer

Interventions

DRUG

Depo-Eligard 7.5 mg

7.5 mg, subcutaneous use

DRUG

Firmagon 120 MG Injection

120 mg, subcutaneous use

DRUG

Firmagon 80 MG Injection

80 mg, subcutaneous use

DRUG

Docetaxel

75 mg per square m, IV infusion

DRUG

Decapeptyl sustained release 11.25 mg

11.25 mg, intramusculair injection

DRUG

Depo-Eligard 45 mg

45 mg, subcutaneous use

DRUG

Depo-Eligard 22.5 mg

22.5 mg, subcutaneous use

DRUG

Darolutamide

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

DRUG

Darolutamide matched placebo

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

RADIATION

Radiotherapy

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

DRUG

Zoladex 3.6Mg Implant

3.6 mg, subcutaneous use

DRUG

Zoladex LA

10.8 mg, subcutaneous use

DRUG

Decapeptyl sustained release 22.5 mg

22.5 mg, intramusculair injection

Sponsors & Collaborators

• Bayer

  collaborator INDUSTRY

• Veracyte, Inc.

  collaborator INDUSTRY

• Cancer Research Antwerp

  lead OTHER

Principal Investigators

• Piet Ost, MD,PhD · Gasthuis Zusters Antwerpen

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-13

Primary Completion

2030-07-31

Completion

2030-12-31

Countries

• Belgium

Study Locations