Trial Title:
Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers
NCT ID:
NCT06282588
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Docetaxel
Goserelin
Triptorelin Pamoate
Leuprolide
Conditions: Keywords:
High-risk
PSMA PET/CT scan
Decipher
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Phase 2: non randomised, 1 treatment arm, open label Phase 3: randomized 1:1 between two
treatment arms, blinded
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
Phase 3 trial: blinded Phase 2 trial: open label
Intervention:
Intervention type:
Drug
Intervention name:
Darolutamide
Description:
2x300 mg tablets twice daily, for up to 96 weeks
Arm group label:
Phase 2 Open Label
Arm group label:
Phase 3 Blinded Experimental
Other name:
Nubeqa
Other name:
BAY1841788
Intervention type:
Drug
Intervention name:
Darolutamide matched placebo
Description:
2x300 mg tablets twice daily, for up to 96 weeks
Arm group label:
Phase 3 Blinded Comparator
Other name:
BAY1841788 matched placebo
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
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
Arm group label:
Phase 2 Open Label
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Intervention type:
Drug
Intervention name:
Zoladex 3.6Mg Implant
Description:
3.6 mg, subcutaneous use
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Goserelin acetate 3.6 mg
Intervention type:
Drug
Intervention name:
Zoladex LA
Description:
10.8 mg, subcutaneous use
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Goserelin acetate 10.8 mg
Intervention type:
Drug
Intervention name:
Decapeptyl sustained release 22.5 mg
Description:
22.5 mg, intramusculair injection
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Triptorelin 11.25 mg
Intervention type:
Drug
Intervention name:
Decapeptyl sustained release 11.25 mg
Description:
11.25 mg, intramusculair injection
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Triptorelin 11.25 mg
Intervention type:
Drug
Intervention name:
Depo-Eligard 45 mg
Description:
45 mg, subcutaneous use
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Leuprorelin acetate 45 mg
Intervention type:
Drug
Intervention name:
Depo-Eligard 22.5 mg
Description:
22.5 mg, subcutaneous use
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Leuprorelin acetate 22.5 mg
Intervention type:
Drug
Intervention name:
Depo-Eligard 7.5 mg
Description:
7.5 mg, subcutaneous use
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Leuprorelin acetate 7.5 mg
Intervention type:
Drug
Intervention name:
Firmagon 120 MG Injection
Description:
120 mg, subcutaneous use
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Degarelix 40 mg
Intervention type:
Drug
Intervention name:
Firmagon 80 MG Injection
Description:
80 mg, subcutaneous use
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Degarelix 20 mg
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
75 mg per square m, IV infusion
Arm group label:
Phase 3 Blinded Comparator
Arm group label:
Phase 3 Blinded Experimental
Other name:
Taxotere
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 (> 0.6) 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 (≤ 0.6), 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.
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 (≤ 0.6) 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 (> 0.6) 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histopathology-proven PCa
2. 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.
3. An Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1.
4. Willingness to undergo a PSMA PET/ CT with or without contrast.
1. 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.
2. 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 [> 0.6] Decipher score is
confirmed) or the non-randomized Phase 2 study (if a low/ intermediate [≤ 0.6]
Decipher score is confirmed).
5. Willingness to have their primary tumor sequenced for determination of Decipher
score
1. Subjects who have a negative PSMA PET/ CT and a tumor with a low/ intermediate
Decipher score (≤ 0.6) will be eligible to enter the non-randomized Phase 2
study.
2. Subjects who have a negative PSMA PET/ CT and a tumor with a high Decipher
score (> 0.6) will be eligible to be randomized to either arm of the Phase 3
study.
3. In subjects with positive PSMA PET/ CT, the Decipher score will not determine
the treatment allocation.
6. Willingness to undergo SOC RT and long-term ADT (treatment with darolutamide and/ or
LHRHA)
7. 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.
8. Subject must be over 18 years of age.
9. Subject able to swallow whole study drug tablets.
10. 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.
11. Adequate organ function determined by the following local laboratory values:
1. 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
2. Adequate renal function: calculated creatinine clearance > 30 mL/min
(Cockroft-Gault)
3. 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)
4. Testosterone levels > 50 ng/dL
Exclusion Criteria:
1. 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)
2. PCa with predominant non-adenocarcinoma features (sarcomatoid or spindle or
neuroendocrine small cell or squamous cell components or other non-adenocarcinoma)
3. Prior pelvic radiotherapy
4. Contraindications for pelvic radiotherapy
5. Contraindications for ADT (treatment with darolutamide and/ or LHRHA)
6. Contraindications or known allergy to PSMA PET/ CT tracers.
7. 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
8. 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.
9. Current use of 5-alpha reductase inhibitor Note: if the alpha reductase inhibitor is
stopped ≥ 2 weeks prior to enrollment, the subject is eligible.
10. Current chronic use of opioid analgesics, for ≥3 weeks for oral or ≥7 days for
non-oral formulations
11. 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)
12. Any condition for which, in the opinion of the Investigator, participation would not
be in the best interest of the subject
13. Major surgery within 21 days prior to enrollment.
14. History of:
1. Loss of consciousness or transient ischemic attack or stroke within 6 months
prior to enrollment, or
2. 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.
15. Known GI disease or GI procedure that could interfere with the oral absorption or
tolerance of darolutamide, including difficulty swallowing tablets
16. 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
17. 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)
18. 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.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
GZA Sint-Augustinus
Address:
City:
Wilrijk
Zip:
2610
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Piet Ost, MD, PhD
Email:
cancertrials@gza.be
Investigator:
Last name:
Piet Ost
Email:
Principal Investigator
Facility:
Name:
OLVZ Aalst
Address:
City:
Aalst
Zip:
9300
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Samuel Br
Investigator:
Last name:
Samuel Bral
Email:
Principal Investigator
Facility:
Name:
AZ Sint-Jan
Address:
City:
Brugge
Zip:
8000
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Sabine Meersschout
Investigator:
Last name:
Sabine Meersschout
Email:
Principal Investigator
Facility:
Name:
Saint Luc
Address:
City:
Bruxelles
Zip:
1200
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Ad Vanderm
Investigator:
Last name:
Ad Vandermeulen
Email:
Principal Investigator
Facility:
Name:
UZA
Address:
City:
Edegem
Zip:
2600
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Karen Fransis
Investigator:
Last name:
Karen Fran
Email:
Principal Investigator
Facility:
Name:
UZ Gent
Address:
City:
Gent
Zip:
9000
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Valérie Fonteyne
Investigator:
Last name:
Valérie Fonteyne
Email:
Principal Investigator
Facility:
Name:
AZ Sint-Lucas
Address:
City:
Gent
Zip:
900
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Lien Van De Voorde
Investigator:
Last name:
Lien Van De Voor
Email:
Principal Investigator
Facility:
Name:
AZ Groeninge
Address:
City:
Kortrijk
Zip:
8500
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Nick Liefhooghe
Investigator:
Last name:
Nick Liefhooghe
Email:
Principal Investigator
Facility:
Name:
CHU Liège
Address:
City:
Liège
Zip:
4000
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Brieuc Suatois
Investigator:
Last name:
Brieuc Sautois
Email:
Principal Investigator
Facility:
Name:
AZ Delta
Address:
City:
Roeselare
Zip:
8800
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Benedikt Engels
Investigator:
Last name:
Benedikt Enge
Email:
Principal Investigator
Facility:
Name:
VITAZ
Address:
City:
Sint-Niklaas
Zip:
9100
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Bart De Troyer
Investigator:
Last name:
Bart De Troyer
Email:
Principal Investigator
Start date:
December 13, 2023
Completion date:
December 31, 2030
Lead sponsor:
Agency:
Cancer Research Antwerp
Agency class:
Other
Collaborator:
Agency:
Bayer
Agency class:
Industry
Collaborator:
Agency:
Veracyte, Inc.
Agency class:
Industry
Source:
Cancer Research Antwerp
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06282588
