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    Summary
    EudraCT Number:2017-002284-18
    Sponsor's Protocol Code Number:UC-0140/1711
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-10-20
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2017-002284-18
    A.3Full title of the trial
    A randomized phase 2 study in patients with triple-negative, androgen receptor positive locally advanced (unresectable) or metastatic breast cancer treated with darolutamide or capecitabine
    Etude de phase II randomisée chez les patientes avec un cancer du sein triple négatif et des récepteurs aux androgènes positifs localement avancé (non résécable) ou métastatique traité par darolutamide ou capécitabine
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    -
    -
    A.3.2Name or abbreviated title of the trial where available
    START
    A.4.1Sponsor's protocol code numberUC-0140/1711
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUNICANCER
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBAYER HealthCare Pharmaceuticals Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUNICANCER
    B.5.2Functional name of contact pointCécile VISSAC-SABATIER
    B.5.3 Address:
    B.5.3.1Street Address101 RUE DE TOLBIAC
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75654 cedex 13
    B.5.3.4CountryFrance
    B.5.4Telephone number33173.76.77.58
    B.5.5Fax number33144.23.55.69
    B.5.6E-mailc-vissac@unicancer.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCapecitabine
    D.3.9.1CAS number 154361-50-9
    D.3.9.3Other descriptive nameCAPECITABINE
    D.3.9.4EV Substance CodeSUB12474MIG
    D.3.10 Strength
    D.3.10.1Concentration unit m2 square meter
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number1100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namedarolutamide
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDAROLUTAMIDE
    D.3.9.1CAS number 1297538-32-9
    D.3.9.4EV Substance CodeSUB185326
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Triple-negative androgen receptor positive (molecular apocrine-like HER2-negative subtype) locally advanced (unresectable) or metastatic breast cancer.
    Cancer du sein triple-négatif avec des récepteurs aux androgènes positifs (sous-type moléculaire apocrine-like HER2-négatif) localement avancé (non résécable) ou métastatique.
    E.1.1.1Medical condition in easily understood language
    -
    -
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to evaluate the antitumour activity of darolutamide or capecitabine in each arm among patients with triple-negative androgen receptor positive advanced/metastatic breast cancer, as measured by the clinical benefit rate at 16 weeks.
    L’objectif primaire est d’estimer l’activité anti-tumorale du darolutamide ou de capécitabine dans chaque bras chez des patientes avec un cancer du sein avancé ou métastatique triple négatif et des récepteurs aux androgènes positifs, en mesurant le taux de bénéfice clinique à la semaine 16.
    E.2.2Secondary objectives of the trial
    Efficacy :
    o Clinical benefit rate at 24 weeks: CR, PR or SD at 24 weeks
    o Objective response rate (ORR) at 16 and 24 weeks
    o Duration of overall response (DoR) at 16 and 24 weeks
    o Overall survival (OS) at 1 and 2 years
    o Progression-free survival (PFS) at 1 and 2 years
    Safety :
    o Tolerance and safety.
    Translational research program :
    o Identification of predictive factors of resistance or sensitivity to the treatment.
    o ctDNA evaluation
    o Pharmacokinetic analysis
    o Additional analyses not listed above could be planned
    Efficacité :
    o Taux de bénéfice clinique à la semaine 24: CR, PR ou SD à la semaine 24
    o Taux de réponse objective aux semaines 16 et 24 (TRO)
    o Durée de la réponse globale aux semaines 16 et 24 (DRG)
    o Survie globale aux années 1 et 2 (SG)
    o Survie sans progression aux années 1 et 2 (SSP)
    Tolérance :
    o Tolérance
    Programme de recherche translationnel :
    o Identification de facteurs prédictifs de la résistance ou de la sensibilité au traitement
    o Evaluation du ctDNA
    o Analyse pharmacocinétique
    o Analyses additionnelles non répertoriées au-dessus pourront être planifiées
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Woman ≥ 18 years old;
    2) Histologically confirmed locally advanced (unresectable) or metastatic breast cancer;
    3) Triple-negative breast cancer:
    Estrogen receptor (ER)-negative and Progesterone receptor (PgR)-negative, as defined by a < 10 % tumor stained cells by immunohistochemistry (IHC); HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative), confirmed centrally before inclusion with FFPE tissue from the primary tumour;
    4) Androgen receptor (AR)-positive, as defined centrally by a ≥ 10% tumor stained cells by IHC
    Note: AR assessment by local pathologist before inclusion is not mandatory;
    5) Patients with a relapse should be chemotherapy naïve or have received a maximum of one line of chemotherapy for advanced disease (providing they are not presenting with life-threatening metastasis); patients could have received adjuvant or neo-adjuvant therapy;
    6) In the exceptional situation of pre-menopausal patient, the addition of a LHRH analog is recommended (androgens might act as an estrogen antagonist in premenopausal patients);
    7) Presence of measurable or evaluable disease according to RECIST v1.1;
    8) ECOG ≤ 1;
    9) Normal hematological function: ANC ≥ 1.500/mm3; platelets count ≥ 100.000/mm3; hemoglobin > 10 g/dL;
    Note: subject must not have received any growth factor within 4 weeks or blood transfusion within 7 days of the hematology laboratory sample obtained at screening)
    10) Normal hepatic function: total bilirubin ≤ 1.5 upper normal limit (UNL) unless this increase is due to a known Gilbert's disease; ASAT and ALAT ≤ 5 UNL (in case of hepatic metastasis);
    11) Creatinine clearance (MDRD formula) ≥ 50 mL/min;
    12) Systolic blood pressure (BP) < 160 mm Hg and diastolic BP < 95 mm Hg, as documented on day of registration/consent (Hypertension allowed provided it is currently controlled);
    13) Cardiac ejection fraction ≥50% measured by MUGA or ECHO done within 4 weeks before inclusion;
    14) For premenopausal patients, patient agreeing to use effective contraception during and for ≥ 6 months after completion of study treatment;
    15) Patient able to comply with the protocol;
    16) Patient must have signed a written informed consent form prior to any study specific procedures;
    17) Patient must be affiliated to a Social Health Insurance.
    1) Femmes âgées ≥ 18 ans;
    2) Cancer du sein localement avancé (non résécable) ou métastatique confirmé histologiquement ;
    3) Cancer du sein triple-négatif:
    Les récepteurs aux oestrogènes (RO)-négatifs et récepteurs aux progestérones (RP)-négatifs, sont définis par un marquage des cellules tumorales < 10 % par immunohistochimie (IHC); le statut HER2 négatif (c.à.d. un score IHC 0 ou 1+, ou un score IHC 2+ et une FISH/SISH/CISH négative), doivent être confirmé en central avant inclusion à partir d’un tissu FFPE provenant de la tumeur primitive;
    4) Récepteurs aux androgènes (RA)-positifs, qui sont définis au niveau central par un marquage cellulaire tumoral par IHC ≥ 10%.
    Note: l’évaluation des RA par un anatomo-pathologiste local avant l’inclusion n’est pas obligatoire;
    5) Les patientes ayant une rechute devront être naïves de chimiothérapie ou avoir reçues au maximum une ligne de chimiothérapie pour la maladie avancée (ne présentant pas métastases potentiellement fatales prouvées); les patientes peuvent avoir reçues de la thérapie adjuvante ou néo-adjuvante;
    6) Dans la situation exceptionnelle où la patiente est pré-ménopausée, l’addition d’un analogue de la LHRH est recommandée (les androgènes pouvant agir comme des antagonistes des oestrogènes chez les patientes pré-ménopausées);
    7) Présence de maladie mesurable ou évaluable selon les critères RECIST v1.1;
    8) ECOG ≤ 1;
    9) Fonction hématologique normale: nombre absolu de polynucléaires neutrophiles ≥ 1.500/mm3; nombre de plaquettes ≥ 100.000/mm3; hémoglobine > 10 g/dL;
    Note: les patientes ne doivent avoir reçu aucun facteur de croissance dans les 4 semaines ou aucune transfusion sanguine dans les 7 jours qui précèdent l’analyse hématologique du screening)
    10) Fonction hépatique normale: bilirubine totale ≤ 1,5 limite normale supérieure (LNS) sauf si cette augmentation est due au syndrome de Gilbert; ASAT et ALAT ≤ 5 LNS (en cas de métastases hépatiques);
    11) Clairance de la créatinine (MDRD formule) ≥ 50 mL/min;
    12) Pression artérielle systolique (PAS) < 160 mm Hg et diastolique (PAD) < 95 mm Hg, comme documenté le jour de l’enregistrement/du consentement (l’hypertension est autorisée si il est prouvé qu’elle est actuellement contrôlée);
    13) Fraction de l’éjection ventriculaire gauche cardiaque ≥50% mesuré par MUGA ou ECHO faite dans les 4 semaines avant l’inclusion;
    14) Pour les patientes pré-ménopausées, les patientes acceptant d’utiliser une méthode de contraception efficace pendant et 6 mois après la fin du traitement de l’étude;
    15) Les patientes doivent être capable de suivre le protocole;
    16) Les patientes doivent avoir signé un consentement éclairé avant toutes procédures spécifiques de l’étude;
    17) Les patientes doivent être affiliées à un régime de sécurité sociale.
    E.4Principal exclusion criteria
    1) HER2-positive status (positivity defined as IHC3+ and/or FISH amplification >2);
    2) Other concurrent malignancies, except adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin; patients who have undergone potentially curative therapy for a prior malignancy are eligible provided there is no evidence of disease for ≥ 5 years and patient is deemed to be at low risk for recurrence;
    3) Active brain metastases or leptomeningeal disease; history of brain metastases allowed provided lesions are stable for at least 3 months as documented by head CT scan or MRI of the brain;
    4) Non-malignant systemic disease, including active infection or concurrent serious illness that would make the patient a high medical risk;
    5) Significant cardiovascular disease, including any of the following:
    a) NYHA class III-IV congestive heart failure
    b) Stroke, unstable angina pectoris, or myocardial infarction within the past 6 months
    c) Severe valvular heart disease
    d) Ventricular arrhythmia requiring treatment;
    6) Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not be included;
    7) Persistent toxicities grade ≥ 2 from any cause, except chemotherapy-induced alopecia and Grade 2 peripheral neuropathy;
    8) Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy;
    9) Any gastrointestinal disorder interfering with absorption of the study drug;
    10) Difficulties with swallowing tablets;
    11) An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease requiring treatment;
    12) Previous treatment with second–generation AR inhibitors such as enzalutamide, ARN–509,
    darolutamide, other investigational AR inhibitors CYP17 enzyme inhibitor such as abiraterone, capecitabine…
    13) Capecitabine is contraindicated for patients with known deficit of dihydropyrimidine dehydrogenase (DPD) activity;
    14) Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy; chemotherapy within the last 3 weeks (6 weeks for nitrosoureas and mitomycin C), or other investigational agents; concurrent palliative radiotherapy is allowed;
    15) Concurrent enrolment in another clinical trial in which investigational therapies are administered;
    16) Pregnant women, women who are likely to become pregnant or are breast-feeding;
    17) Patients with 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;
    18) Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol;
    19) Individual deprived of liberty or placed under the authority of a tutor.
    1) Statut HER2-positif (la positivité est défini par un IHC3+ et/ou une amplification par FISH >2);
    2) D’autres cancers, à l’exception de l’épithélioma basocellulaire cutané, du carcinome à cellules squameuses de la peau ou de l’épithélioma in situ du col utérin traités de façon adéquate; les patientes qui auront reçues un traitement potentiellement curatif pour un cancer antérieur sont éligibles s’il n’y a aucune évidence de maladie depuis au moins 5 ans et qu’elles sont considérées comme ayant un faible risque de récurrence;
    3) Des métastases actives du cerveau ou une maladie lepto-méningée; un antécédent de métastases au cerveau est permis si les lésions sont stables depuis au moins 3 mois et documentés par un CT scan de la tête ou une IRM du cerveau;
    4) Maladie systémique non maligne, incluant les infections actives ou des pathologies concomitantes sérieuses qui pourraient faire courir aux patientes un risque médical très élevé;
    5) Maladie cardiovasculaire significative, incluant une des raisons suivantes:
    a) Insuffisance cardiaque congestive de classe III-IV selon le NYHA
    b) Un accident vasculaire cérébral, une angine de poitrine instable, ou un infarctus du myocarde dans les 6 derniers mois
    c) Cardiopathie valvulaire sévère
    d) Arythmie ventriculaire nécessitant un traitement;
    6) Patientes avec des problèmes héréditaires d’intolérance au galactose, un déficit en lactase de Lapp ou un syndrome de malabsorption du glucose ou du galactose (maladies héréditaires rares) ne doivent pas être inclues ;
    7) Toxicités persistantes d’un grade ≥ 2 quel qu’en soit la cause, sauf l’alopécie chimio-induit et un grade 2 de neuropathie périphérique;
    8) Maladie auto-immune active ou non contrôlée nécessitant un traitement par corticostéroïdes;
    9) Tous désordres gastro-intestinaux pouvant interférer avec l’absorption des traitements de l’étude;
    10) Difficulté à avaler les comprimés de l’étude;
    11) Une hépatite virale active, un HIV connu avec une charge virale détectable, ou une maladie chronique du foie qui nécessiterait un traitement;
    12) Antécédent de traitement par des inhibiteurs des AR de seconde génération comme
    l’enzalutamide ARN–509, darolutamide, autres inhibiteurs des AR en cours d’investigation, inhibiteur de l’enzyme CYP17 comme l’abiraterone, la capécitabine… ;
    13) La capécitabine est contre-indiquée chez les patientes connue pour un déficit de l’activité de la déshydrogénase di-hydropyrimidine (DPD) (voir section 4.4);
    14) Tout traitement anticancéreux antérieurs, y compris la radiothérapie, les hormonothérapies, l’immunothérapie ; la chimiothérapie dans les 3 dernières semaines (6 semaines pour les nitrosourées et la mitomycin C), ou d’autres médicaments expérimentaux; une radiothérapie simultanée à visée palliative est autorisée;
    15) Une inclusion simultanée dans un autre essai clinique dans lequel un traitement expérimental est administré;
    16) Femmes enceintes, femmes qui désirent une grossesse ou allaitantes;
    17) Patientes avec des problèmes psychologiques, familiaux, sociologiques ou des conditions géographiques qui pourraient entraver la compliance des visites et des suivis prévus par le protocole. Ces conditions doivent être discutés avec le patient avant l’inclusion dans l’essai clinique;
    18) Patientes avec une histoire de non-compliance des traitements médicaux ou en incapacité de suivre un protocole;
    19) Individu privé de leur droits ou placé sous une autorité de tutelle.
    E.5 End points
    E.5.1Primary end point(s)
    For each arm (Arm n°1: darolutamide / Arm n°2: capecitabine):
    The primary endpoint is based on clinical benefit rate at 16 weeks. The clinical benefit rate (CBR) is the measurement of all patients who have a complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks (CBR16) according to RECIST v1.1
    Pour chaque bras (Bras n°1: darolutamide / Bras n°2: capécitabine):
    Le critère primaire est basé sur le taux de bénéfice clinique à la semaine 16. Le taux de bénéfice clinique (CRB) sera mesuré sur toutes les patientes qui auront une réponse complète (CR), une réponse partielle (PR) ou une maladie stable (SD) à la semaine 16 (CRB16) selon les critères RECIST v1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    -
    -
    E.5.2Secondary end point(s)
    For each arm (Arm n°1: darolutamide / Arm n°2: capecitabine):
    Efficacy:
    - Clinical benefit rate at 24 weeks (CBR24)
    - Objective response rate (ORR) at 16 and 24 weeks: The Objective response is defined as complete response (CR) or partial response (PR) according to RECIST v1.1.
    - Duration of overall response (DoR) at 16 and 24 weeks: The DoR is defined as the time from documentation of tumour response (CR/PR) to disease progression, according to RECIST v1.1.
    - Overall Survival (OS) at 1 and 2 years: The OS is defined as the time from the first administration of treatment to death from any cause.
    - Progression-free survival (PFS) at 1 and 2 years: The PFS is defined as the time from the first administration of treatment to progression or death of any cause, whichever occurs first.
    Safety:
    - Evaluation of Toxicity in each arm
    Safety will be evaluated by type, frequency and severity of adverse drug reactions according to NCI-CTC (v4.03): In order to be considered evaluable for toxicity, patients should have received at least one dose of treatment.
    Translational studies:
    Tumor samples (mandatory from the primary tumor; in addition every effort should be made to biopsy metastatic sites). A variety of methodologies will be applied including gene expression profiling, and next generation sequencing (NGS).
    One blood sample will be taken in each patient for constitutional DNA isolation. Plasma samples will be collected for ctDNA detection (optional research).
    A mandatory pharmacokinetic analysis will be conducted in selected study centers and requires blood sampling at 2, 4 and 6 h after the first intake of darolutamide.
    Additional analyses will be defined by the study steering committee at the end of the trial.
    Pour chaque bras (Bras n°1: darolutamide / Bras n°2: capécitabine):
    Efficacité:
    - Taux de bénéfice clinique à la semaine 24 (CBR24)
    - Taux de réponse objectif (TRO) aux semaines 16 et 24: La réponse objective est définie comme une réponse complète (CR) ou une réponse partielle (PR) selon les critères RECIST v1.1.
    - Durée de la réponse complète (DRC) aux semaines 16 et 24: La DRC est définie par le temps entre la documentation du réponse tumorale (CR/PR) jusqu’à la progression de la maladie, selon les critères RECIST v1.1.
    - Survie globale (SG) aux années 1 et 2: l’OS est définie par le temps entre la première administration du traitement jusqu’au décès quel qu’en soit la cause.
    - Survie sans progression (SSP) aux années 1 et 2 : La PFS est définie par le temps entre la première administration du traitement jusqu’à la progression ou le décès quel qu’en soit la cause, selon l’évènement survenant en premier.
    Tolérance:
    - Evaluation de la toxicité dans chacun des bras
    La tolérance sera évaluée selon le type, la fréquence et la sévérité des évènements indésirables selon le NCI-CTC (v4.03): Pour être considéré dans cette analyse de toxicité, les patientes devront avoir reçues au moins une dose de traitement.
    Etudes translationnelles:
    Echantillons tumoraux (obligatoire pour la tumeur primitive, de plus tous les efforts devront être fait pour faire une biopsie des sites métastatiques). Une variété d’analyses sera utilisée incluant les profils d’expression génique et le séquençage de dernière génération (NGS).
    Un échantillon sanguin devra être prélevé à chaque patiente pour l’isolement de l’ADN constitutionnel. Des échantillons plasmatiques seront collectés pour la détection du ctDNA (recherche optionnelle).
    Une analyse pharmacocinétique obligatoire sera réalisée dans tous les sites et elle nécessite le prélèvement dd’échantillons sanguins à 2h, 4h et 6h suivant la première prise de darolutamide.
    Des analyses additionnelles seront définies par le comité de pilotage en fin d’étude.
    E.5.2.1Timepoint(s) of evaluation of this end point
    -
    -
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned40
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months42
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state90
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    none
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-10-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-12-02
    P. End of Trial
    P.End of Trial StatusOngoing
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