Metastasis-directed therapy, whether or not in combination with hormone therapy, in patients with prostate cancer recurrence after initial treatment and a maximum of 5 metastases.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

25 Apr 2022 → ongoing

Decision date (initial)

2023-03-07

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-502373-42-00

EudraCT number

2022-000066-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The aim is to investigate whether the addition of short-term ADT during 1 month or short-term ADT during 6 months together with an androgen receptor targeted therapy (ARTA) to MDT significantly prolongs PMFS and/or mCRPC-FS. Metastatic castration-refractory prostate cancer free survival (mCRPCFS) will be calculated from the last day of MDT until the first day of
diagnosis of castration-resistant prostate cancer (CRPC). CRPC is defined according to the contemporary EAU-guidelines as the time to biochemical and/or clinical progression at castrate testosterone levels (< 50 ng/dl). BcR is defined as two consecutive PSA rises (1 week interval), each with a value ≥ 25% increase above the nadir PSA level after treatment, and both with a PSA higher than the baseline PSA at inclusion in the study.

Secondary objectives 5

1. Biochemical progression-free survival will be calculated from the last day of MDT until the first day of biochemical relapse (BcR). BcR is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of > 2 ng/ml and a rise of 50% above the nadir PSA level.
2. Clinical progression free survival will be calculated from the last day of MDT until the first day of progression on PSMA PET-CT/MRI. - Cancer specific survival will be calculated from last day of treatment until PCa death.
3. Overall survival will be calculated from last day of treatment until death from any cause.
4. Acute and late toxicity as a result of radiotherapy will be scores using the Common Toxicity Criteria Version 5.0.
5. Quality of life scoring using the EORTC QLQ-C30 supplement with QLQPR25. We will assess the quality-of-life-years with the EuroQOL classification system (EQ-5D-5L).

Conditions and MedDRA coding

Oligorecurrent hormone-sensitive prostate cancer patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
3. Histologically proven initial diagnosis of prostatic adenocarcinoma.
4. Priory treated and controlled primary tumor.
5. Biochemical recurrence defined by prostate-specific antigen (PSA) values >0.2 ng/ml (i.e., two consecutive increases) following radical prostatectomy + postoperative radiotherapy and a PSA value of 2 ng/ml above the nadir after high-dose RT.
6. Oligorecurrent disease defined as a maximum of 5 extracranial metastases in any organ, diagnosed on PSMA PET-CT or PSMA PET-MRI reported according to the E-PSMA consensus guidelines for interpretation of PSMA-PET. Nodal (N1) disease can be included only when accompanied by M1a-c disease, provided that the total number of spots does not exceed 5.
7. Serum testosterone ≥ 50 ng/dl or 1.7 nmol/L (above castration level).
8. WHO performance 0-2
9. Age >= 18 years old
10. Absence of psychological, sociological or geographical condition potentially hampering compliance with study protocol.
11. Patients must be presented at the multidisciplinary board meeting and the inclusion in the trial needs approval by this board. All participants that are considered for Trial participation, per the above criteria will be documented on the Screening Log, including Screen Failures.

Exclusion criteria 10

1. Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
2. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
3. Participation in an interventional Trial with an investigational medicinal product (IMP) or device.
4. Serum testosterone level at castration level (< 50 ng/dl or 1.7 nmol/L).
5. PSA rise while on active treatment (LHRH-agonist, LHRH antagonist, anti-androgen, maximal androgen blockade, oestrogen).
6. Presence of poly-metastatic disease, defined as more than 5 metastatic lesions.
7. Active malignancy other than prostate cancer that could potentially interfere with the interpretation of this trial.
8. Previous treatments (RT, surgery) or comorbidities rendering new treatment with SBRT impossible.
9. Contra indications for intake of enzalutamide (seizure or any condition that may predispose to seizure; significant cardiovascular disease within the last three months including myocardial infarction, unstable angina, congestive heart failure, ongoing arrythmias of grade >2 or a thromboembolic event).
10. Not able to understand the treatment protocol or sign informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Poly-metastatic free survival will be calculated from the last day of MDT until the first day of poly-progression which is defined as the detection > 5 new lesions at PSMA PET-CT/MRI. In case of poly-progression, pADT will be considered the standard-of-care. Other indications to start pADT are local progression of an irradiated site and/or clinical symptoms caused by local progression.

Secondary endpoints 7

1. Metastatic castration-refractory prostate cancer free survival (mCRPC-FS). mCRPC-FS will be calculated from the last day of MDT until the first day of diagnosis of castration-resistant prostate cancer (CRPC). CRPC is defined according to the contemporary EAU-guidelines as the time to biochemical and/or clinical progression at castrate testosterone levels (< 50 ng/dl).
2. Biochemical progression-free survival (bPFS) will be calculated from the last day of the first SBRT or from the day metastasectomy was performed until the first day of biochemical relapse (BcR). BcR is defined as two consecutive PSA rises (1 week interval), each with a value ≥ 25% increase above the nadir PSA level after treatment, and both with a PSA higher than the baseline PSA at inclusion in the study. Patients free from BCR are censored at their last follow-up.
3. Clinical progression free survival (cPFS) will be calculated from the last day of MDT until the first day of progression (local, nodal or metastatic) on PSMA PET-CT/MRI. Imaging is performed in case of BcR. Progression on PSMA PET-CT/MRI will be defined as in the consensus statements on PSMA PET-CT/MRI response assessment criteria in prostate cancer.
4. Cancer specific survival (CSS) will be calculated from last day of treatment until PCa death.
5. Overall survival (OS) will be calculated from last day of treatment until death from any cause.
6. Acute and late toxicity as a result of radiotherapy will be scores using the Common Toxicity Criteria Version 5.0 (30). Toxicity will be scored at every follow-up visit.
7. Quality of life scoring using the EORTC QLQ-C30 supplement with QLQPR25. We will assess the quality-of-life-years with the EuroQOL classification system (EQ-5D-5L). Assessments are planned at baseline, last day of treatment, and during follow-up consultation at month M1, M3, M6, M12 and M24.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 12

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Co-Investigator

Public contact point

Organisation

UZ Leuven

Contact name

Investigator

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications