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Prostate CancerPhase 2DARTNCT04641078

Stereotactic Body Radiotherapy With or Without Darolutamide for OligoRecurrent Prostate Cancer

A Phase 2 study testing Darolutamide and metastasis-directed treatment in people with Prostate Cancer and Prostate Cancer Recurrent, run by University Hospital, Ghent at 8 sites in Belgium.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The current trial will test the combination of darolutamide with SBRT, in oligometastatic recurrent hormone sensitive prostate cancer. We hypothesize that the addition of short-term darolutamide improves metastasis-free survival when added to SBRT without a detrimental impact on the QoL. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Darolutamide and metastasis-directed treatment
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
8 sitesBelgium
Study dates
12 Feb 2021to 12 Feb 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven initial diagnosis of adenocarcinoma of the prostate
  • 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.
  • 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.
  • 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.
  • 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 positive19.
  • Asymptomatic for metastatic PCa
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  • Age >= 18 years
  • WHO class 0-1
  • 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
  • Before patient registration/randomization, written informed consent must be given in accordance with to ICH/GCP, and national/local regulations.

Who cannot join

  • Local relapse in the prostate gland or prostate bed not suitable for a local salvage treatment
  • Small cell carcinoma of the prostate
  • PSA doubling time >12 months
  • Serum testosterone level <50ng/dl or 1.7 nmol/L at time of randomization
  • 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
  • Spinal cord compression or impending spinal cord compression
Show all 11Show fewer
  • Metastases in previously irradiated areas precluding safe delivery of SBRT
  • Contraindications to darolutamide
  • Previous treatment with cytotoxic agent for PCa
  • Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,…)
  • Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years.

Trial locations and contacts

8 sites in 1 country.

Piet Ost, MD, PhD contact

003293323015

piet.ost@ugent.be

8 sites in 1 country

Belgium8 sites, 8 recruiting

  • OLVZ Aalst

    Aalst

    Ruben De Groote, MD

    Recruiting

  • GZA

    Antwerp

    Piet Dirix, MD

    Recruiting

  • AZ St-Jan Brugge

    Bruges

    Sabine Meersschout, MD

    Recruiting

  • Institut Jules Bordet

    Brussels

    François-Xavier Otte, MD

    Recruiting

  • AZ St-Lucas Gent

    Ghent

    Lien Van De Voorde, MD

    Recruiting

  • Ghent University Hospital

    Ghent

    Piet Ost, MD, PhD

    Recruiting

  • Jessa Ziekenhuis

    Hasselt

    Leen Noé, MD

    Recruiting

  • AZ Groeninge

    Kortrijk

    Siska Van Bruwaene, MD

    Recruiting

Other trials in Belgium

About this study

Official title: Stereotactic Body Radiotherapy With or Without Darolutamide for OligoRecurrent Prostate Cancer: a Randomized Phase II Trial (DART)

The current trial will test the combination of darolutamide with SBRT, in oligometastatic recurrent hormone sensitive prostate cancer. We hypothesize that the addition of short-term darolutamide improves metastasis-free survival when added to SBRT without a detrimental impact on the QoL. Considering the large reluctance of both patients and physicians to be randomized to observation, we propose to use the historical data from previous reported randomized trials (STOMP and ORIOLE) as a comparator to explore as a secondary endpoint.

Read the detailed description

As of the 2018 EAU guidelines, PSMA PET-CT is now recommended for prostate cancer patients with a rising PSA following local therapy, resulting in an increase in patients with conventional imaging M0, but novel imaging M1-state. This creates a new class of patients for which no clear guidelines exist on the optimal management. It became clear that there is no real consensus nor data on how these patients should be treated.

In 1995, a new approach was proposed, hypothesizing that patients with a limited number of metastases (oligometastases) might benefit from eradication of metastases by means of local therapy, or metastasis-directed therapy. Stereotactic body radiotherapy (SBRT), a novel radiotherapy technique for metastatic and primary prostate cancer treatments, has emerged as a highly precise radiotherapy method able to eradicate small metastases with acceptable toxicity. Nevertheless, responses following SBRT were not always durable. To improve response rates and time to new metastases, additional steps should be taken balancing with potential added toxicity. One of the logical steps would be to combine SBRT with temporary androgen deprivation therapy (ADT) as this combination therapy is standard of care for primary PCa and locally recurrent PCa17. However, ADT, negatively impacts quality of life (QoL) even when used temporary. Anti-androgen or androgen receptor (AR) pathway inhibitors (ARpI) may circumvent these side effects by suppressing AR transcription by competitive inhibition of AR, without lowering systemic testosterone. The current trial will test the combination of darolutamide with SBRT, in oligometastatic recurrent hormone sensitive prostate cancer. We hypothesize that the addition of short-term darolutamide improves metastasis-free survival when added to SBRT without a detrimental impact on the QoL.

Being tested
Darolutamide, metastasis-directed treatment
Keywords
Radiotherapy, Metastasis-directed therapy, Oligometastatic recurrent hormone sensitive prostate cancer
Medical subject headings
Prostatic Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarolutamideDrug

    600 mg BID

  • metastasis-directed treatmentRadiation

    stereotactic body radiotherapy

Study groups in NCT04641078
Study groupRoleWhat they receive
Arm AExperimentalSBRT + 6 months of darolutamide (600 mg b.i.d.)
Receives: Drug: Darolutamide; Radiation: metastasis-directed treatment
Arm BOtherSBRT only
Receives: Radiation: metastasis-directed treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Metastasis-free survival

    Metastasis-free survival is defined as time between randomization and the appearance of a new metastatic recurrence (any M1) as suggested by PET-CT or death due to any cause.

    Measured: 2 year

Secondary outcomes (10)

  1. Clinical progression-free survival

    Clinical progression-free survival is defined as the time between randomization and the appearance of a new lesion (any N1 or M1), a local recurrence as suggested by PET-CT, symptoms related to progressive PCa, or death due to any cause.

    Measured: 2 year

  2. Biochemical relapse-free survival

    For patients who had previous RP at initial diagnosis, a biochemical recurrence is defined by any confirmed PSA rise above 0.20 ng/ml with a confirmatory rise at least 2 weeks later. For patients who had previous RT to the prostate at initial diagnosis, a biochemical recurrence is defined as the nadir + 2ng/ml (Phoenix definition). Non-responders are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA

    Measured: 2 year

  3. Time to next systemic therapy

    Time to next systemic therapy is defined as the initiation of any PCa systemic treatment. Systemic therapy will typically be initiated on progression and/or development of new metastases, but indications are at the discretion of the physician.

    Measured: 4 year

  4. Castrate resistant-free survival

    Time to castration resistant disease is defined as the time from trial randomization until castration resistant status

    Measured: 4 year

  5. Prostate cancer-specific survival

    PCa-specific survival will be read as the time from trial randomization to the date of death due to PCa.

    Measured: 4 year

  6. Overall survival

    Overall survival will be read as the time from trial randomization to the date of death from any cause.

    Measured: 4 year

  7. Toxicity: acute toxicity

    Radiotherapy toxicity will be assessed according to NCI CTCAE v5.0.

    Measured: 3 months

  8. Toxicity: late toxicity

    Radiotherapy toxicity will be assessed according to NCI CTCAE v5.0.

    Measured: 2 year

  9. Patient reported QOL as per EORTC-QLQ C30

    Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients. A higher score of a symptom scale or item indicates a worse condition; a higher score of a functional scale or global health status/QoL indicates a better condition. A clinically meaningful change is defined as a change from baseline of at least 10 points (i.e., about one-half standard deviation) in either direction.

    Measured: 2 year

  10. Patient reported QOL as per EORTC-QLQ PR25

    Validated questionnaire assessing the health-related QOL of prostate cancer patients. A higher score of a symptom scale or item indicates a worse condition; a higher score of a functional scale or global health status/QoL indicates a better condition. A clinically meaningful change is defined as a change from baseline of at least 10 points (i.e., about one-half standard deviation) in either direction.

    Measured: 2 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2020
  2. Study start12 Feb 2021
  3. Primary completion12 Feb 2026 (estimated)
  4. Study completion12 Feb 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
124 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04641078
Sponsor's protocol ID
BC-06863
Acronym
DART
Status last verified
Feb 2024
First submitted
17 Nov 2020
Last updated
28 Feb 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Morgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, Chou R, Jacene HA, Kamran SC, Kim SK, Kirkby E, Luckenbaugh AN, Nathanson BJ, Nyame YA, Posadas EM, Tran PT, Chen RC. Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions. J Urol. 2024 Apr;211(4):526-532. doi: 10.1097/JU.0000000000003890. Epub 2024 Feb 29.

    PubMed 38421252

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Darolutamide and metastasis-directed treatment in people with Prostate Cancer and Prostate Cancer Recurrent, run by University Hospital, Ghent at 8 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Piet Ost, MD, PhD (003293323015, piet.ost@ugent.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Metastasis-free survival (time frame: 2 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04641078, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.

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