Evaluation of the impact of metastasis-directed therapy in patients with castration-refractory prostate cancer and a maximum of 5 progressive lesions.

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

18 Dec 2023 → ongoing

Decision date (initial)

2023-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The aim is to investigate whether the addition of metastasis-directed therapy will increase overall survival as compared to standard of care treatment in patients with oligoprogressive metastatic castration-refractory prostate cancer. Overall survival will be calculated from the day of randomization until death from any cause.

Secondary objectives 5

1. Quality of life (QOL): Quality of life scoring using the EORTC QLQ-C30 supplement with QLQ-PR25. We will assess the quality-of-life-years with the EuroQOL classification system (EQ-5D-5L). Assessments are planned at baseline and during follow-up consultation at month M1, M3, M6, M12 and M24.
2. Cancer specific survival: Cancer specific survival (CSS) will be calculated from the day of randomization until PCa death.
3. Radiographic progression free survival: Radiographic progression free survival will be calculated from the day of randomization until the first day of progression (local, nodal or metastatic) on conventional imaging or PSMA PET-CT. rPFS will be determined using the same imaging modality employed at baseline. Imaging is performed every 6 months during follow-up or at any time in case of PSA progression or symptoms.
4. Metastasis-directed therapy induced acute and late toxicity scoring: Acute and late toxicity as a result of radiotherapy will be scored using the Common Toxicity Criteria Version 5.0 (21). Toxicity will be scored at every follow-up visit.
5. Cost-effectiveness of metastasis-directed therapy in patients with oligoprogressive metastatic castration-refractory prostate cancer.

Conditions and MedDRA coding

Oligoprogressive metastatic castration-refractory prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 true secsual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)), use of condom or vasectomy or commitment to a partner using implants, injectables, combined oral contraceptives or some IUDs (27). This method of contraception needs to be continued for at least 6 months after the last dose of Trial treatment(s).
3. Oligoprogressive disease defined as a maximum of 5 extracranial progressive lesions (pre-existing lesions, the development of new lesions, or both) in any organ reported according to the PROMISE V2 Framework for the standardized reporting of PSMA PET for research and clinical routine. In case of locally persistent/recurrent disease, a diagnostic magnetic resonance imaging (MRI) or dedicated CT-scan should be performed. If a metastatis in the extremities is suspected, a bone scan or dedicated CT-scan will be performed. In case of locally persistent/recurrent disease, a diagnostic MRI of the prostate (bed) and/or biopsy of the site is recommended. There are two different mCRPC patient groups who are eligible for inclusion in the trial: a. Patients with oligoprogressive disease with pADT only as ongoing treatment (Type 1). b. Patients with oligoprogressive disease with pADT +/- second line systemic therapy. This is both the combination of pADT + ARTA as ongoing treatment or patients who had received docetaxel in the past (Type 2).
4. Castration-refractory disease, defined as testosterone level < 50 ng/dL or 1.7 nmol/L and the presence of biochemical or radiologic progression.
5. Prior treatment of the primary tumor by radiotherapy or surgery. If the primary tumor had not been treated, local therapy should be added to the treatment together MDT.
6. WHO performance 0-2
7. Age 18 years or older
8. Absence of psychological, sociological or geographical condition potentially hampering compliance with study protocol.
9. Patients must be presented at the multidisciplinary board meeting and the inclusion in the trial needs approval by this board
10. Acinar adenocarcinoma (inclusive neuro-endocrine dedifferentiation).

Exclusion criteria 12

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 > 50 ng/ml or 1.7 nmol/l.
5. Presence of poly-progressive disease, defined as more than 5 progressive lesions on PSMA PET-CT including local recurrence, nodal disease and/or metastatic lesions.
6. Active malignancy other than prostate cancer that could potentially interfere with the interpretation of this trial.
7. Previous treatments (RT, surgery) or comorbidities rendering new treatment with SBRT impossible.
8. Not able to understand the treatment protocol or sign informed consent.
9. Patients already treated with radionuclides, cabazitaxel or PARP-inhibitors in the past.
10. Ductal adenocarcinoma and small-cell prostate cancer
11. Spinal bone lesion that is highly symptomatic, neurologically threatening or at risk of fracture will be excluded.
12. Patients with progressive disease while receiving docetaxel at the moment of progression.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) will be calculated from the day of randomization until death from any cause.

Secondary endpoints 6

1. Quality of life (QOL): Quality of life scoring using the EORTC QLQ-C30 supplement with QLQ-PR25. We will assess the quality-of-life-years with the EuroQOL classification system (EQ-5D-5L). Assessments are planned at baseline and during follow-up consultation at month M1, M3, M6, M12 and M24.
2. Cancer specific survival: Cancer specific survival (CSS) will be calculated from the day of randomization until PCa death.
3. Radiographic progression free survival: Radiographic progression free survival will be calculated from the day of randomization until the first day of progression (local, nodal or metastatic) on conventional imaging or PSMA PET-CT. rPFS will be determined using the same imaging modality employed at baseline. Imaging is performed every 6 months during follow-up or at any time in case of PSA progression or symptoms.
4. Metastasis-directed therapy induced acute and late toxicity scoring: Acute and late toxicity as a result of radiotherapy will be scored using the Common Toxicity Criteria Version 5.0 (21). Toxicity will be scored at every follow-up visit.
5. Cost-effectiveness of metastasis-directed therapy in patients with oligoprogressive metastatic castration-refractory prostate cancer.
6. 18F PSMA PET-CT prediciton value in patients with oligoprogressive metastatic castration-refractory prostate cancer.

Investigational products

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

Test 11

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

Co-Investigator

Locations

1 EU/EEA country · 9 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 24 files

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

Application history

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