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

NCT05346848 | Recruiting Phase 2 DMC

• 2 other identifiers: IB 2021-03AFU-GETUG P15
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Prostate Cancer

Keywords

unfavorable intermdiate risk prostate cancer; androgen deprivation therapy; radiation therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (31)

• Assessment of efficacy in terms of biological response at the end of darolutamide or ADT

  An expected average of 6 months

• 2-month biological response

  2 months after randomization

• 3-month biological response

  3 months after the end of radiotherapy

• 6-month biological response

  6 months after the end of radiotherapy

• 9-month biological response

  9 months after the end of radiotherapy

Study Arms (2)

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

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

Drug: Association of ADT and EBRT

Interventions

Association of darolutamide and EBRT DRUG

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

Experimental Arm A: combination of radiotherapy and darolutamide

Association of ADT and EBRT DRUG

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

Standard Arm B: combination of radiotherapy and androgen deprivation therapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male patients with prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• ≥ 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,

You may not qualify if:

• 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.
• 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,
• 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,

Sponsors & Collaborators

• Institut Bergonié: lead
• Bayer: collaborator

Study Sites (10)

Sainte Catherine, Institut du Cancer Avignon-Provence

Avignon, 84918, France

NOT YET RECRUITING

CHRU Besançon

Besançon, 25030, France

NOT YET RECRUITING

Institut Bergonie

Bordeaux, 33076, France

RECRUITING

CHRU Brest - Hôpital Morvan

Brest, 29200, France

NOT YET RECRUITING

Assitance Publique des Hôpitaux de Marseille - CHU La Timone

Marseille, 13385, France

NOT YET RECRUITING

Hôpital de la Pitié Salpétrière

Paris, 75651, France

NOT YET RECRUITING

CHP Saint-Grégoire

Saint-Grégoire, 35760, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, 44805, France

NOT YET RECRUITING

IUCT Oncopôle

Toulouse, 31059, France

NOT YET RECRUITING

Clinique Pasteur

Toulouse, 31076, France

NOT YET RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

Paul SARGOS, MD

CONTACT

+33556333333; p.sargos@bordeaux.unicancer.fr

Simone MATHOULIN-PELISSIER, MD, PhD

CONTACT

s.mathoulin@bordeaux.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2022
• First Posted: April 26, 2022
• Study Start: February 24, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2030
• Last Updated: October 2, 2025

Record last verified: 2025-10

Locations

FR (10)