Prostate CancerPhase 2DARIUSNCT05346848
Randomized Phase II Trial on Short Term Darolutamide Concomitant to Radiation Therapy for Patients With Intermediate Unfavorable Risk Prostate Cancer
A Phase 2 study testing Association of darolutamide and EBRT and Association of ADT and EBRT in people with Prostate Cancer, run by Institut Bergonié at 10 sites in France.
Trial summary
Randomized non-comparative phase II trial to assess the preliminary signs of antitumor activity of darolutamide plus radiation therapy in patients with unfavorable intermediate risk prostate cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Association of darolutamide and EBRT and Association of ADT and EBRT
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 10 sitesFrance
- Study dates
- 24 Feb 2023to Feb 2030
- Phase
- Phase 2
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
- Age ≥ 18,
- Histological diagnosis of prostate malignancy cancer
- Cancer without loco-regional or distant metastasis (tumor assessment must comprise at least Pelvic MRI AND thoraco-abdomino-pelvic contrast-enhanced CT-Scan AND Bone Scintigraphy. (Note that additional assessment by PET-Scan is allowed as per investigator judgement),
- Unfavorable intermediate risk prostate cancer diagnosis defined by the NCCN Guidelines.
- One of the following criteria is sufficient to define an unfavorable intermediate risk prostate cancer:
- Gleason = 7 (4+3)
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- ≥ 50% of thecore of biopsies need to be positive for adenocarcinoma
- If these criteria are not being identified, two or three of the following criteria are necessary to define unfavorable intermediate risk prostate cancer:
- PSA value between 10-20 ng/ml
- Gleason 7 (3+4) or 6
- T2b (clinical or radiological) Note: patients with iT3a can be included only if gleason score is 6 and PSA less than 20 .
- Patients newly diagnosed with an unfavorable intermediate risk prostate cancer according to the protocol criteria or previously diagnosed with low risk (Gleason score < 6, clinical stage < T2a, and PSA< 10) prostate cancer progressing to eligible risk disease according to the protocol criteria within 30 days before registration
- Patients must have a life expectancy of at least 5 years,
- Performance status ECOG ≤ 2,
- Patients without contra-indications to EBRT as per physician judgement,
- Patients with adequate organ function defined by all the following laboratory values
- Available archived paraffin-embedded tumor sample for research purpose,
- Patients with a social security in compliance with the french law,
- Voluntary signed and dated written informed consent prior to any study specific procedure,
- Men must agree to use an effective method of contraception throughout the treatment period and for one week after discontinuation of treatment.
Who cannot join
- Stage T3b-T4 prostate cancer by clinical examination or radiologic evaluation,
- Patients with Gleason score ≥8,
- Patients with PSA >20 ng/ml,
- Presence of loco-regional or distant metastasis,
- Contra-indications to MRI and to contrast-enhanced CT-scan,
- Hypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL or below the normal range for the institution.
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- Previous prostate cancer treated by androgen deprivation, chemotherapy, surgery, or radiotherapy,
- Patients with previous orchiectomy
- Patients actively receiving or having received within 6 months prior enrollment any concurrent androgens, anti-androgens, estrogens, or progestational agents,
- Patients having received ketoconazole, finasteride or dutasteride within 30 days of inclusion,
- Previous and current malignancies other than prostate cancer within the last 5 years with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, acute lymphoblastic leukemia, non-muscle invasive bladder cancer,
- Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection),
- History of cerebrovascular accident (within the last 6 months)
- Impaired cardiac function as defined in the Protocol
- Uncontrolled hypertension
- Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of study drug,
- Major surgery within 4 weeks prior enrolment except pelvic lymph-nodes dissection,
- Known hypersensitivity to any involved study drug or of its formulation components, to natural gonadotrophin releasing hormone or its analogues
- Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome
- Men who are not using an effective method of contraception as previously described
- Use of herbal or alternative remedies that may affect hormonal status such as Prostasol or PC-SPES,
- History of non-compliance to medical regimens or inability to grant consent,
- Patient unable to follow and comply with the study procedures because of any geographical, social or psychpsychological reasons,
- Individuals under judicial protection or deprived of liberty.
- Inability to swallow or to give subcutaneous or intramuscular injections.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Simone MATHOULIN-PELISSIER, MD, PhD contact
10 sites in 1 country
France10 sites, 10 recruiting
- Not yet recruiting
Sainte Catherine, Institut du Cancer Avignon-Provence
Avignon, 84918
Lysian CARTIER, MD, l.cartier@isc84.org
- Not yet recruiting
CHRU Besançon
Besançon, 25030
Jihane BOUSTANI, MD, jboustani@chu-besancon.fr
- Recruiting
Institut Bergonie
Bordeaux, 33076
Paul SARGOS, MD, p.sargos@bordeaux.unicancer.fr
Guilhem ROUBAUD, MD, g.roubaud@bordeaux.unicancer.fr
- Not yet recruiting
CHRU Brest - Hôpital Morvan
Brest, 29200
Ulrike SCHICK, MD, PhD, ulrike.schick@chu-brest.fr
- Not yet recruiting
Assitance Publique des Hôpitaux de Marseille - CHU La Timone
Marseille, 13385
Xavier MURACCIOLE, MD, xavier.muraccole@ap-hm.fr
- Not yet recruiting
Hôpital de la Pitié Salpétrière
Paris, 75651
Jean-Marc SIMON, MD, PhD, jean-marc.simon@aphp.fr
- Not yet recruiting
CHP Saint-Grégoire
Saint-Grégoire, 35760
Xavier ARTIGNAN, MD, xartignan@vivalto-sante.com
- Not yet recruiting
Institut de Cancérologie de l'Ouest - Site René Gauducheau
Saint-Herblain, 44805
Stéphane SUPIOT, MD, PhD, stephane.supiot@ico.unicancer.fr
- Not yet recruiting
IUCT Oncopôle
Toulouse, 31059
Jonathan KHALIFA, MD, kahlifa.jonathan@iuct-oncopole.fr
- Not yet recruiting
Clinique Pasteur
Toulouse, 31076
Igor LATORZEFF, MD, i.latorzeff@clinique-pasteur.com
About this study
Official title: A Randomized Non-comparative Phase II Multicentric Trial on Short Term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients With Intermediate Unfavorable Risk Prostate Cancer
Randomized non-comparative phase II trial to assess the preliminary signs of antitumor activity of darolutamide plus radiation therapy in patients with unfavorable intermediate risk prostate cancer.
Read the detailed description
Multicentric randomized non-comparative, open-label, phase II trial, based on signle-stage design, to assess the preliminary signs of antitumor activity of darolutamide plus radiation therapy in patients with unfavorable intermediate risk prostate cancer.
Patients satisfying eligibility criteria will be randomized according to 2 treatment modalities
- Arm A (experimental arm): combination of external beam radiotherapy (EBRT) and 6 months darolutamide.
- Arm B (standard arm): combination of external beam radiotherapy (EBRT) and 6 months ADT (androgen deprivation therapy)
Two patients randomized in arm A for one patient randomized in arm B.
- Conditions
- Prostate Cancer
- Being tested
- Association of darolutamide and EBRT, Association of ADT and EBRT
- Keywords
- unfavorable intermdiate risk prostate cancer, androgen deprivation therapy, radiation therapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Association of darolutamide and EBRTDrug
Darolutamide will be taken orally at a fixed dose of 600 mg twice daily (1200 mg), on a continuous basis, for a maximum of 6 months. Darolutamide will start at Day 1.
- External Beam Radiotherapy (EBRT) will start two months after treatment initiation. All patients will be treated with standard schedules:
- 78 Gy with classical 2 Gy/fractions, 5 days/7
- Or 60 Gy with 3 Gy/fractions, 5 days/7
- Use of IMRT and IGRT is mandatory
- Clinical Target Volume Definition according to GETUG Guidelines
- Organ at risk dose constraints according to RECORAD
Association of ADT and EBRTDrug
Treatment by Androgen Deprivation Therapy (ADT) will be prescribed as per market authorization and following investigator judgement. ADT treatment will consist on:
- Either LH-RH agonist injection given every 3 months for 6 months, or once for 6 months,
- Either LH-RH antagonist given monthly for 6 months
External Beam Radiotherapy (EBRT) will start two months after treatment initiation. All patients will be treated by high dose irradiation in stereotactic conditions:
- 78 Gy with classical 2 Gy/fractions, 5 days/7
- Or 60 Gy with 3 Gy/fractions, 5 days/7
- Use of IMRT and IGRT is mandatory
- Clinical Target Volume Definition according to GETUG Guidelines
- Organ at risk dose constraints according to RECORAD
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm A: combination of radiotherapy and darolutamide | Experimental | Patients with unfavorable intermediate risk prostate cancer will be treated with darolutamide for a maximum of 6 months combined with external beam radiotherapy Receives: Drug: Association of darolutamide and EBRT |
| Standard Arm B: combination of radiotherapy and androgen deprivation therapy | Other | Patients with unfavorable intermediate risk prostate cancer will be treated with androgen deprivation therapy (ADT) as per market authorization combined with external beam radiotherapy Receives: Drug: Association of ADT and EBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of efficacy in terms of 6-month biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 6 months after randomization
Secondary outcomes (31)
Assessment of efficacy in terms of biological response at the end of darolutamide or ADT
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: An expected average of 6 months
2-month biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 2 months after randomization
3-month biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 3 months after the end of radiotherapy
6-month biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 6 months after the end of radiotherapy
9-month biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 9 months after the end of radiotherapy
2-year biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 2 years after randomization
3-year biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 3 years after randomization
5-year biological response
Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria
Measured: 5 years after randomization
2-year biochemical progression-free survival (bPFS)
Biochemical progression-free survival is defined as the delay between the date of randomization and the date of biochemical disease progression or death, whichever comes first.
Measured: 2 years
3-year biochemical progression-free survival (bPFS)
Biochemical progression-free survival is defined as the delay between the date of randomization and the date of biochemical disease progression or death, whichever comes first.
Measured: 3 years
5-year biochemical progression-free survival (bPFS)
Biochemical progression-free survival is defined as the delay between the date of randomization and the date of biochemical disease progression or death, whichever comes first.
Measured: 5 years
2-year metastasis free survival (MFS)
Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)
Measured: 2 years
3-year metastasis free survival (MFS)
Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)
Measured: 3 years
5-year metastasis free survival (MFS)
Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)
Measured: 5 years
2-year disease free survival (DFS)
Disease free survival is defined as the delay between the date of randomization and the first of the following events: biological PSA progression defined as level higher than PSA nadir + 2ng/mL according to Phoenix's criteria ; progression (local, regional, distant) or death (any cause)
Measured: 2 years
3-year disease free survival (DFS)
Disease free survival is defined as the delay between the date of randomization and the first of the following events: biological PSA progression defined as level higher than PSA nadir + 2ng/mL according to Phoenix's criteria ; progression (local, regional, distant) or death (any cause)
Measured: 3 years
5-year disease free survival (DFS)
Disease free survival is defined as the delay between the date of randomization and the first of the following events: biological PSA progression defined as level higher than PSA nadir + 2ng/mL according to Phoenix's criteria ; progression (local, regional, distant) or death (any cause)
Measured: 5 years
2-year prostate cancer-specific survival (PCSS)
Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death
Measured: 2 years
3-year prostate cancer-specific survival (PCSS)
Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death
Measured: 3 years
5-year prostate cancer-specific survival (PCSS)
Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death
Measured: 5 years
2-year overall survival (OS)
Overall survival is defined as the delay between the date of randomization and the date of death (all cause).
Measured: 2 years
3-year overall survival (OS)
Overall survival is defined as the delay between the date of randomization and the date of death (all cause).
Measured: 3 years
5-year overall survival (OS)
Overall survival is defined as the delay between the date of randomization and the date of death (all cause).
Measured: 5 years
Time to testosterone recovery
Time to testosterone recovery defined as the time from randomization to the time when serum of total testosterone level increases to above the lower limit of the normal range.
Measured: An expected average of 6 months
Acute safety profile independently for each treatment strategy
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
Measured: 3 months
Late 2-year safety profile independently for each treatment strategy
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
Measured: 2 years
Late 3-year safety profile independently for each treatment strategy
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
Measured: 3 years
Late 5-year safety profile independently for each treatment strategy
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
Measured: 5 years
Assessment of quality of life
Quality of life will be assessed as per the EORTC QLQ-C30 questionnaire and prostate cancer module PR-25
Measured: Throughout the follow-up period, an expected average of 5 years
Assessment of erectile dysfunction
Erectile dysfunction will be assessed as per IIEF5
Measured: Throughout the follow-up period, an expected average of 5 years
Assessment of symptoms of benign prostatic hyperplasia
Symptoms of benign prostatic hyperplasia will be assessed as per IPSS
Measured: Throughout the follow-up period, an expected average of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2022
- Study start24 Feb 2023
- Primary completionDec 2026 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Bergonié
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05346848
- Sponsor's protocol ID
- IB 2021-03
- Other IDs
- 2023-509494-23-00, AFU-GETUG P15, 2023
- Acronym
- DARIUS
- Status last verified
- Oct 2026
- First submitted
- 21 Apr 2022
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No