Randomized Phase II Trial on Short Term Darolutamide Concomitant to Radiation Therapy for Patients With Intermediate Unfavorable Risk Prostate Cancer (DARIUS)

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Association of darolutamide and EBRT; Drug: Association of ADT and EBRT

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.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Paul SARGOS, MD; Phone Number: +33556333333; Email: p.sargos@bordeaux.unicancer.fr
• Study Contact Backup: Name: Simone MATHOULIN-PELISSIER, MD, PhD; Email: s.mathoulin@bordeaux.unicancer.fr

Study Locations

• France
  • Avignon, France, 84918
    • Not yet recruiting
    • Sainte Catherine, Institut du Cancer Avignon-Provence
    • Contact: Lysian CARTIER, MD; Email: l.cartier@isc84.org
  • Besançon, France, 25030
    • Not yet recruiting
    • CHRU Besançon
    • Contact: Jihane BOUSTANI, MD; Email: jboustani@chu-besancon.fr
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonie
    • Contact: Guilhem ROUBAUD, MD; Email: g.roubaud@bordeaux.unicancer.fr
    • Contact: Paul SARGOS, MD; Email: p.sargos@bordeaux.unicancer.fr
  • Brest, France, 29200
    • Not yet recruiting
    • CHRU Brest - Hopital Morvan
    • Contact: Ulrike SCHICK, MD, PhD; Email: ulrike.schick@chu-brest.fr
  • Marseille, France, 13385
    • Not yet recruiting
    • Assitance Publique des Hôpitaux de Marseille - CHU La Timone
    • Contact: Xavier MURACCIOLE, MD; Email: xavier.muraccole@ap-hm.fr
  • Paris, France, 75651
    • Not yet recruiting
    • Hopital de la Pitie Salpetriere
    • Contact: Jean-Marc SIMON, MD, PhD; Email: jean-marc.simon@aphp.fr
  • Saint-Grégoire, France, 35760
    • Not yet recruiting
    • CHP Saint-Gregoire
    • Contact: Xavier ARTIGNAN, MD; Email: xartignan@vivalto-sante.com
  • Saint-Herblain, France, 44805
    • Not yet recruiting
    • Institut de Cancérologie de l'Ouest - Site René Gauducheau
    • Contact: Stéphane SUPIOT, MD, PhD; Email: stephane.supiot@ico.unicancer.fr
  • Toulouse, France, 31059
    • Not yet recruiting
    • IUCT Oncopole
    • Contact: Jonathan KHALIFA, MD; Email: kahlifa.jonathan@iuct-oncopole.fr
  • Toulouse, France, 31076
    • Not yet recruiting
    • Clinique Pasteur
    • Contact: Igor LATORZEFF, MD; Email: i.latorzeff@clinique-pasteur.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18,
2. Histological diagnosis of prostate malignancy cancer
3. 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),

4. 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)
   • ≥ 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 .
5. 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
6. Patients must have a life expectancy of at least 5 years,
7. Performance status ECOG ≤ 2,
8. Patients without contra-indications to EBRT as per physician judgement,
9. Patients with adequate organ function defined by all the following laboratory values
10. Available archived paraffin-embedded tumor sample for research purpose,
11. Patients with a social security in compliance with the french law,
12. Voluntary signed and dated written informed consent prior to any study specific procedure,
13. Men must agree to use an effective method of contraception throughout the treatment period and for one week after discontinuation of treatment.

Exclusion Criteria:

1. Stage T3b-T4 prostate cancer by clinical examination or radiologic evaluation,
2. Patients with Gleason score ≥8,
3. Patients with PSA >20 ng/ml,
4. Presence of loco-regional or distant metastasis,
5. Contra-indications to MRI and to contrast-enhanced CT-scan,
6. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL or below the normal range for the institution.
7. Previous prostate cancer treated by androgen deprivation, chemotherapy, surgery, or radiotherapy,
8. Patients with previous orchiectomy
9. Patients actively receiving or having received within 6 months prior enrollment any concurrent androgens, anti-androgens, estrogens, or progestational agents,
10. Patients having received ketoconazole, finasteride or dutasteride within 30 days of inclusion,
11. 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,
12. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection),
13. History of cerebrovascular accident (within the last 6 months)
14. Impaired cardiac function as defined in the Protocol
15. Uncontrolled hypertension
16. Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of study drug,
17. Major surgery within 4 weeks prior enrolment except pelvic lymph-nodes dissection,
18. Known hypersensitivity to any involved study drug or of its formulation components, to natural gonadotrophin releasing hormone or its analogues
19. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome
20. Men who are not using an effective method of contraception as previously described
21. Use of herbal or alternative remedies that may affect hormonal status such as Prostasol or PC-SPES,
22. History of non-compliance to medical regimens or inability to grant consent,
23. Patient unable to follow and comply with the study procedures because of any geographical, social or psychpsychological reasons,
24. Individuals under judicial protection or deprived of liberty.
25. Inability to swallow or to give subcutaneous or intramuscular injections.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm A: combination of radiotherapy and darolutamide; Patients with unfavorable intermediate risk prostate cancer will be treated with darolutamide for a maximum of 6 months combined with external beam radiotherapy	Drug: Association of darolutamide and EBRT; 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
Other: Standard Arm B: combination of radiotherapy and androgen deprivation therapy; Patients with unfavorable intermediate risk prostate cancer will be treated with androgen deprivation therapy (ADT) as per market authorization combined with external beam radiotherapy	Drug: Association of ADT and EBRT; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	2 months after randomization
3-month biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	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	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	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	2 years after randomization
3-year biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	3 years after randomization
5-year biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	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.	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.	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.	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)	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)	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)	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)	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)	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)	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	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	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	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).	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).	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).	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.	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	3 months
Late 2-year safety profile independently for each treatment strategy	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5	2 years
Late 3-year safety profile independently for each treatment strategy	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5	3 years
Late 5-year safety profile independently for each treatment strategy	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5	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	Throughout the follow-up period, an expected average of 5 years
Assessment of erectile dysfunction	Erectile dysfunction will be assessed as per IIEF5	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	Throughout the follow-up period, an expected average of 5 years

Collaborators and Investigators

• Sponsor: Institut Bergonié
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: radiation therapy; androgen deprivation therapy; unfavorable intermdiate risk prostate cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: IB 2021-03; AFU-GETUG P15 (Other Identifier: AFU GETUG)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No