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    Summary
    EudraCT Number:2019-000678-41
    Sponsor's Protocol Code Number:ET19-006
    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:2019-03-07
    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 number2019-000678-41
    A.3Full title of the trial
    CABRAMET - A phase 2 study of cabozantinib in renal cell carcinoma (mRCC) with brain metastases
    CABRAMET - Etude de phase 2 évaluant le cabozantinib dans le traitement du carcinome à cellules rénales métastatique (mRCC) avec métastases cérébrales
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of cabozantinib in renal cell carcinoma with brain metastases
    Etude évaluant le cabozantinib dans le traitement du carcinome à cellules rénales métastatique avec métastases cérébrales
    A.3.2Name or abbreviated title of the trial where available
    CABRAMET
    CABRAMET
    A.4.1Sponsor's protocol code numberET19-006
    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 SponsorCentre Léon Bérard
    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 supportIpsen Pharma
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCentre Léon Bérard
    B.5.2Functional name of contact pointDRCI
    B.5.3 Address:
    B.5.3.1Street Address28 rue Laennec
    B.5.3.2Town/ cityLYON Cedex 08
    B.5.3.3Post code69373
    B.5.3.4CountryFrance
    B.5.4Telephone number+33478 78 29 67
    B.5.5Fax number+33478 78 27 15
    B.5.6E-mailellen.blanc@lyon.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.2.1.1.1Trade name Cabozantinib
    D.2.1.1.2Name of the Marketing Authorisation holderCABOMETYX
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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 Coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    Metastatic renal cell carcinoma with non locally pre-treated brain metastases, in first line treatment or after one or two prior treatments.
    Carcinome à cellules rénales métastatique avec métastases cérébrales non prétraitées localement, en traitement de première intention ou après un ou deux traitements antérieurs.
    E.1.1.1Medical condition in easily understood language
    Metastatic renal cancer with brain metastases.
    Cancer du rein localement avancé avec des métastases cérébrales.
    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
    To evaluate the non progression rate in brain metastases at 3 months.
    Evaluer le taux de non progression des métastases cérébrales à 3 mois.
    E.2.2Secondary objectives of the trial
    • Safety of cabozantinib,especially in terms of neurological tolerance (NCI-CTCAE),
    • Best response in brain metastases (RANO-BM criteria),
    • Response rate on the extra-cranial disease at 3 months (RECIST v1.1),
    • Progression-free survival (PFS), measured from the date of inclusion to the date of first documented disease progression or death from any cause,
    • Overall survival (OS), measured from the date of inclusion to the date of death from any cause).
    • Tolérance, notamment neurologique (NCI-CTCAE),
    • Meilleure réponse au niveau des métastases cérébrales (critères RANO-BM),
    • Taux de réponse sur la maladie extra-cérébrale à 3 mois (RECIST v1.1),
    • Survie sans progression (PFS), mesurée depuis la date d’inclusion jusqu’à la date de 1ère progression ou de décès quelle qu’en soit la cause,
    • Survie globale, mesurée depuis la date d’inclusion jusqu’à la date de décès quelle qu’en soit la cause.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Biomarkers (serum and plasma samples). MET expression in available tumor.
    Biomarqueurs (sérum et plasma). Expression de MET dans la tumeur archivée disponible.
    E.3Principal inclusion criteria
    I1. Age ≥ 18 years.
    I2. Histologically proven mRCC.
    I3. Brain metastases not requiring corticosteroids at dose > 40 mg/day.
    I4. At least 1 brain lesion ≥8 mm in longest diameter or >5 mm if > 1 lesion.
    I5. Not previously treated by cabozantinib.
    I6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1.
    I7. Life expectancy ≥ 3 months
    I8. Adequate organ function as defined by the following criteria.
    - Total serum bilirubin 2 x ULN (Gilbert’s disease exempted)
    - Serum transaminases and alkaline phosphatases 2.5 x ULN, or in case of liver or bone metastasis 5 x ULN
    - Serum creatinine 2 x ULN, creatinine clearance 50 ml/min
    - Absolute neutrophil count (ANC) 1 500/mm3
    - Platelets 100 000/mm3 (100 G/l)
    - Hemoglobin 9.0 g/dl.
    I9. Covered by a medical/health insurance.
    I10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
    ...See the protocol
    I1. Age ≥ 18 ans.
    I2. mRCC histologiquement prouvé.
    I3. Métastases cérébrales ne nécessitant pas un traitement par corticoïdes à une dose > 40 mg/jour.
    I4. Au moins une lésion cérébrale de plus long diamètre ≥8 mm ou >5 mm si > 1 lésion.
    I5. Non antérieurement traité par cabozantinib.
    I6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1.
    I7. Espérance de vie ≥ 3 mois.
    I8. Paramètres biologiques adéquats selon les critères suivants/ Fonctions médullaire, rénale et hépatique adéquates définies par les valeurs biologiques suivantes :
    - Bilirubine
    - Totale ≤ 2 x ULN (sauf en cas de maladie de Gilbert),
    -Transaminases sériques et phosphatases alcalines ≤ 2.5 x ULN, ou ≤ 5.0 x LSN en cas de métastases hépatiques ou osseuses.
    - Créatinine sérique ≤ 2 x ULN, clairance de la créatinine 50 ml/min
    - Polynucléaires neutrophiles (PNN) 1 500/mm3
    - Plaquettes 100 000/mm3 (100 G/l)
    - Hémoglobine 9.0 g/dl.
    I9. Affiliation à un régime d’assurance maladie (ou bénéficiaire d’un tel régime).
    I10. Volonté et capacité de se conformer au calendrier des visites, schéma de traitements, examens et autres procédures prévues dans l’étude.
    ...Voir Protocole
    E.4Principal exclusion criteria
    E1. Any local previous treatment of current brain metastases.
    E2. Any anti-coagulation therapy (except preventive treatment at low dose).
    E3. Contra-indication for MRI (i.e. pace-maker).
    E4. Uncontrolled seizures.
    E5. Any symptoms of intracranial hypertension.
    E6. Any of the following within 12 months prior to treatment initiation: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, ischemic or hemorrhagic stroke including transient ischemic attack.
    E7. Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical treatment.
    E8. Ongoing cardiac dysrhythmia of grade 2, atrial fibrillation of any grade, QTc interval > 0.43.
    E9. Pregnant or breast feeding woman (mandatory negative serum or urinary pregnancy test at study entry for all women of childbearing potential).
    E10. Any acute or chronic medical or psychiatric condition or laboratory abnormality that would make the patient unsuited to study participation.
    ...See the protocol
    E1. Tout traitement local antérieur des présentes métastases cérébrales.
    E2. Tout traitement anticoagulant (sauf traitement préventif à faible dose).
    E3. Contre-indication à l’IRM (i.e. pacemaker).
    E4. Crises épileptiques non contrôlées.
    E5. Tout symptôme d’hypertension intracrânienne.
    E6. Toute affection cardiovasculaire parmi les suivantes dans les 12 derniers mois précédant l’initiation du traitement : angor instable/sévère, infarctus du myocarde, pontage coronarien, Insuffisance cardiaque congestive symptomatique, accident vasculaire ischémique ou hémorragique incluant les accidents ischémiques transitoires.
    E7. Hypertension non contrôlée, définie par pression artérielle systolique >150 mmHg ou diastolique >90 mmHg, malgré un traitement médical approprié/optimal.
    E8. Dysrhythmie cardiaque en cours de grade ≥ 2, fibrillation auriculaire de tout grade, intervalle QT corrigé > 0.43.
    E9. Femme enceinte ou allaitant (test de grossesse sérique ou urinaire négatif obligatoire à l’inclusion pour les femmes en âge de procréer.
    E10. Toute affection médicale ou psychiatrique chronique ou aigue ou anomalie biologique pouvant rendre le patient inadapté à la participation à l’étude.
    ...Voir protocole
    E.5 End points
    E.5.1Primary end point(s)
    Non progression rate in brain metastases at 3 months
    Le taux de non progression des métastases cérébrales à 3 mois
    E.5.1.1Timepoint(s) of evaluation of this end point
    Tumor assessment in brain will be performed by central review according to the RANO-BM criteria.
    L'évaluation de la tumeur dans le cerveau sera effectuée par une revue centrale selon les critères de RANO-BM.
    E.5.2Secondary end point(s)
    • Incidence of adverse events (AEs) assessed using the National Cancer Institute – Common Terminology Criteria for Adverse Event (NCI-CTCAE) v5 grading scale, specific registration of neurological event during study duration,
    • Best response in brain metastases, evaluated according to RANO-BM criteria,
    • Response on the extracranial disease, evaluated according to RECIST v1.1 criteria,
    • PFS, measured from the date of inclusion to the date of first documented disease progression or death from any cause. Patients without event will be censored at the time of the last clinical evaluation.
    • OS, measured from the date of inclusion to the date of death from any cause;
    • Incidence des effets indésirables (EI) évaluée à l’aide de l’échelle de notation v5 de l’Institut national du cancer - Critères communs de terminologie pour les effets indésirables (NCI-CTCAE) v5, enregistrement spécifique de l’événement neurologique pendant la durée de l’étude,
    • Meilleure réponse en métastases cérébrales, évaluée selon les critères de RANO-BM,
    • Réponse à la maladie extra crânienne, évaluée selon les critères de RECIST v1.1,
    • Survie sans progression , mesurée à partir de la date d'inclusion jusqu'à la date de la première documentation de la progression de la maladie ou du décès, quelle qu'en soit la cause. Les patients sans événement seront censurés lors de la dernière évaluation clinique.
    • Survie globale, mesurée à partir de la date d'inclusion jusqu'à la date du décès, quelle qu'en soit la cause.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Evaluating according to :
    • NCI-CTCAE
    • RANO-BM
    • RECIST v1.1
    •date of inclusion to the date of first documented disease progression or death from any cause.
    Evaluation selon les critères suivants :
    • NCI-CTCAE
    • RANO-BM
    • RECIST v1.1
    • date d'inclusion jusqu'à la date de la première documentation de la progression de la maladie ou du décès quelle qu'en soit la cause
    • date d'inclusion jusqu'à la date du décès, quelle qu'en soit la cause.
    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 No
    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 No
    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 trial1
    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 concerned25
    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 No
    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
    Dernière visite du dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months6
    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: 38
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 39
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    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 state77
    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)
    After the end of the trial, treatment plan will be decided by each investigator.
    Après la fin de l'essai, chaque investigateur décidera du plan de traitement.
    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 Decision2019-04-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-05-13
    P. End of Trial
    P.End of Trial StatusOngoing
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