Stereotactic body radiotherapy with or without Darolutamide for OligoRecurrent prostate cancer: a randomized phase II trial (DART)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Ziekenhuis Gent

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Feb 2021 → 16 Apr 2026

Decision date (initial)

2024-04-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511140-37-00

EudraCT number

2019-004952-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To compare (radiographic) metastasis-free survival (rPFS) between SBRT plus darolutamide and SBRT only for oligorecurrent PCa.

Secondary objectives 8

1. To describe the toxicity of both arms in patients with oligometastatic disease.
2. To determine local control after SBRT + darolutamide in patients with oligometastatic disease.
3. To assess biochemical relapse-free survival (BRFS) in both arms.
4. To assess clinical progression-free survival (PFS) in both arms.
5. To assess time to next systemic therapy in both arms
6. To assess CRPC-free survival in both arms
7. To assess PCa-specific and overall survival in both arms.
8. To assess quality of life in both arms.

Conditions and MedDRA coding

OligoRecurrent prostate cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically proven initial diagnosis of adenocarcinoma of the prostate
2. Biochemical relapse of PCa following radical local prostate treatment (radical prostatectomy (RP), primary radiotherapy or the combination of RP and prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2018.
3. Following RP, patients with a biochemical relapse are eligible in case a metastatic relapse is detected even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage). In the absence of prior prostate bed radiotherapy, prostate bed radiotherapy is mandatory for all pT3a or higher or patients with a positive margin at time of RP.
4. For patients without prior RP that have a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence. Patients with a confirmed local recurrence and metastases are eligible in case they also undergo a local salvage therapy.
5. Metastatic relapse on PSMA PET-CT with a maximum of 5 metastases (any M1a, M1b or M1c). Concomitant diagnosis of N1 disease is allowed as long as all lesions are treated with SBRT and the total number of lesions does not exceed 5. PSMA positive lesions will be scored using the MI-RADS scoring system with lesions scored 4 or 5 considered positive.
6. Asymptomatic for metastatic PCa
7. Age >=18 years
8. WHO class 0-1
9. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
10. Before patient registration/randomization, written informed consent must be given in accordance with to ICH/GCP, and national/local regulations.

Exclusion criteria 11

1. Local relapse in the prostate gland or prostate bed not suitable for a local salvage treatment
2. Small cell carcinoma of the prostate
3. PSA doubling time >12 months
4. Serum testosterone level <50ng/dl or 1.7 nmol/L at time of randomization
5. Currently receiving ADT or PSA rise while on active treatment with ADT (LHRH-agonist, LHRH-antagonist, anti-androgen or estrogen) within the past 6 weeks
6. Spinal cord compression or impending spinal cord compression
7. Metastases in previously irradiated areas precluding safe delivery of SBRT
8. Contraindications to darolutamide
9. Previous treatment with cytotoxic agent for PCa
10. Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,…)
11. Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Metastasis-free survival

Secondary endpoints 8

1. Clinical progression-free survival
2. Biochemical relapse-free survival
3. Time to next systemic therapy
4. Castrate resistant-free survival
5. Prostate cancer-specific survival
6. Overall survival
7. Acute and late toxicity
8. Quality of life

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Ziekenhuis Gent

Sponsor organisation

Universitair Ziekenhuis Gent

Address

Corneel Heymanslaan 10

City

Gent

Postcode

9000

Country

Belgium

Scientific contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Prof. Dr. Piet Ost

Public contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Prof. Dr. Piet Ost

Locations

1 EU/EEA country · 8 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 16 files

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

Application history

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