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

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ClinicalTrials.gov Identifier: NCT05346848
Recruitment Status : Not yet recruiting
First Posted : April 26, 2022
Last Update Posted : October 6, 2022
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Institut Bergonié

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Association of darolutamide and EBRT Drug: Association of ADT and EBRT Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 2022
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : November 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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

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




Primary Outcome Measures :
  1. Assessment of efficacy in terms of 6-month biological response [ Time Frame: 6 months after randomization ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria


Secondary Outcome Measures :
  1. Assessment of efficacy in terms of biological response at the end of darolutamide or ADT [ Time Frame: An expected average of 6 months ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  2. 2-month biological response [ Time Frame: 2 months after randomization ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  3. 3-month biological response [ Time Frame: 3 months after the end of radiotherapy ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  4. 6-month biological response [ Time Frame: 6 months after the end of radiotherapy ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  5. 9-month biological response [ Time Frame: 9 months after the end of radiotherapy ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  6. 2-year biological response [ Time Frame: 2 years after randomization ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  7. 3-year biological response [ Time Frame: 3 years after randomization ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  8. 5-year biological response [ Time Frame: 5 years after randomization ]
    Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria

  9. 2-year biochemical progression-free survival (bPFS) [ Time Frame: 2 years ]
    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.

  10. 3-year biochemical progression-free survival (bPFS) [ Time Frame: 3 years ]
    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.

  11. 5-year biochemical progression-free survival (bPFS) [ Time Frame: 5 years ]
    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.

  12. 2-year metastasis free survival (MFS) [ Time Frame: 2 years ]
    Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)

  13. 3-year metastasis free survival (MFS) [ Time Frame: 3 years ]
    Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)

  14. 5-year metastasis free survival (MFS) [ Time Frame: 5 years ]
    Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)

  15. 2-year disease free survival (DFS) [ Time Frame: 2 years ]
    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)

  16. 3-year disease free survival (DFS) [ Time Frame: 3 years ]
    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)

  17. 5-year disease free survival (DFS) [ Time Frame: 5 years ]
    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)

  18. 2-year prostate cancer-specific survival (PCSS) [ Time Frame: 2 years ]
    Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death

  19. 3-year prostate cancer-specific survival (PCSS) [ Time Frame: 3 years ]
    Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death

  20. 5-year prostate cancer-specific survival (PCSS) [ Time Frame: 5 years ]
    Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death

  21. 2-year overall survival (OS) [ Time Frame: 2 years ]
    Overall survival is defined as the delay between the date of randomization and the date of death (all cause).

  22. 3-year overall survival (OS) [ Time Frame: 3 years ]
    Overall survival is defined as the delay between the date of randomization and the date of death (all cause).

  23. 5-year overall survival (OS) [ Time Frame: 5 years ]
    Overall survival is defined as the delay between the date of randomization and the date of death (all cause).

  24. Time to testosterone recovery [ Time Frame: An expected average of 6 months ]
    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.

  25. Acute safety profile independently for each treatment strategy [ Time Frame: 3 months ]
    Toxicity graded using the Common Terminology Criteria for Adverse Events version 5

  26. Late 2-year safety profile independently for each treatment strategy [ Time Frame: 2 years ]
    Toxicity graded using the Common Terminology Criteria for Adverse Events version 5

  27. Late 3-year safety profile independently for each treatment strategy [ Time Frame: 3 years ]
    Toxicity graded using the Common Terminology Criteria for Adverse Events version 5

  28. Late 5-year safety profile independently for each treatment strategy [ Time Frame: 5 years ]
    Toxicity graded using the Common Terminology Criteria for Adverse Events version 5

  29. Assessment of quality of life [ Time Frame: Throughout the follow-up period, an expected average of 5 years ]
    Quality of life will be assessed as per the EORTC QLQ-C30 questionnaire and prostate cancer module PR-25

  30. Assessment of erectile dysfunction [ Time Frame: Throughout the follow-up period, an expected average of 5 years ]
    Erectile dysfunction will be assessed as per IIEF5

  31. Assessment of symptoms of benign prostatic hyperplasia [ Time Frame: Throughout the follow-up period, an expected average of 5 years ]
    Symptoms of benign prostatic hyperplasia will be assessed as per IPSS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male patients with prostate cancer
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05346848


Contacts
Layout table for location contacts
Contact: Paul SARGOS, MD +33556333333 p.sargos@bordeaux.unicancer.fr
Contact: Simone MATHOULIN-PELISSIER, MD, PhD s.mathoulin@bordeaux.unicancer.fr

Locations
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France
Sainte Catherine, Institut du Cancer Avignon-Provence
Avignon, France, 84918
Contact: Lysian CARTIER, MD       l.cartier@isc84.org   
CHRU Besançon
Besançon, France, 25030
Contact: Jihane BOUSTANI, MD       jboustani@chu-besancon.fr   
Institut Bergonie
Bordeaux, France, 33076
Contact: Paul SARGOS, MD       p.sargos@bordeaux.unicancer.fr   
Contact: Guilhem ROUBAUD, MD       g.roubaud@bordeaux.unicancer.fr   
CHRU Brest - Hôpital Morvan
Brest, France, 29200
Contact: Ulrike SCHICK, MD, PhD       ulrike.schick@chu-brest.fr   
Assitance Publique des Hôpitaux de Marseille - CHU La Timone
Marseille, France, 13385
Contact: Xavier MURACCIOLE, MD       xavier.muraccole@ap-hm.fr   
Hôpital de la Pitié Salpétrière
Paris, France, 75651
Contact: Jean-Marc SIMON, MD, PhD       jean-marc.simon@aphp.fr   
CHP Saint-Grégoire
Saint-Grégoire, France, 35760
Contact: Xavier ARTIGNAN, MD       xartignan@vivalto-sante.com   
Institut de Cancérologie de l'Ouest - Site René Gauducheau
Saint-Herblain, France, 44805
Contact: Stéphane SUPIOT, MD, PhD       stephane.supiot@ico.unicancer.fr   
IUCT Oncopôle
Toulouse, France, 31059
Contact: Jonathan KHALIFA, MD       kahlifa.jonathan@iuct-oncopole.fr   
Clinique Pasteur
Toulouse, France, 31076
Contact: Igor LATORZEFF, MD       i.latorzeff@clinique-pasteur.com   
Sponsors and Collaborators
Institut Bergonié
Bayer
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Responsible Party: Institut Bergonié
ClinicalTrials.gov Identifier: NCT05346848    
Other Study ID Numbers: IB 2021-03
AFU-GETUG P15 ( Other Identifier: AFU GETUG )
First Posted: April 26, 2022    Key Record Dates
Last Update Posted: October 6, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut Bergonié:
unfavorable intermdiate risk prostate cancer
androgen deprivation therapy
radiation therapy
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases