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    The EU Clinical Trials Register currently displays   42869   clinical trials with a EudraCT protocol, of which   7063   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2012-004550-28
    Sponsor's Protocol Code Number:AIO-NET-0112
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-10-14
    Trial results View 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 ConcernedGermany - BfArM
    A.2EudraCT number2012-004550-28
    A.3Full title of the trial
    EVINEC: Safety and Tolerability of Everolimus as second-line treatment in poorly differentiated neuroendocrine carcinoma / neuroendocrine carcinoma G3 according to WHO 2010 and neuroendocrine tumor G3 - an investigtor initiated Phase II study.
    EVINEC: Sicherheit und Verträglichkeit von Everolimus in der Zweitlinientherapie bei schlecht differenziertem neuroendokrinen Karzinom / neuroendokrinem Karzinom G3 (WHO 2010) und neuroendokrinem Tumor G3 – eine Arzt-initiierte Phase II Studie.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    EVINEC: Safety and Tolerability of Everolimus as second-line treatment in poorly differentiated neuroendocrine carcinoma / neuroendocrine carcinoma G3 according to WHO 2010 and neuroendocrine tumor G3 - an investigtor initiated Phase II study.
    A.3.2Name or abbreviated title of the trial where available
    EVINEC
    A.4.1Sponsor's protocol code numberAIO-NET-0112
    A.5.4Other Identifiers
    Name:Novartis-Nr: Number:CRAD001KDE55T
    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 SponsorAIO-Studien-gGmbH
    B.1.3.4CountryGermany
    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 supportAIO-Studien-gGmbH
    B.4.2CountryGermany
    B.4.1Name of organisation providing supportNovartis Pharma GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAIO-Studien-gGmbH
    B.5.2Functional name of contact pointSponsor
    B.5.3 Address:
    B.5.3.1Street AddressKuno-Fischer-Straße 8
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code14057
    B.5.3.4CountryGermany
    B.5.4Telephone number+4930814534431
    B.5.5Fax number+4930322932926
    B.5.6E-mailinfo@aio-studien-ggmbh.de
    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 Afinitor 2,5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Pharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.9.1CAS number 159351-69-6
    D.3.9.3Other descriptive nameEVEROLIMUS
    D.3.9.4EV Substance CodeSUB02065MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2,5
    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 Yes
    D.2.1.1.1Trade name Afinitor 5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Pharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.9.1CAS number 159351-69-6
    D.3.9.3Other descriptive nameEVEROLIMUS
    D.3.9.4EV Substance CodeSUB02065MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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
    • Poorly differentiated neuroendocrine carcinoma, neuroendocrine carcinoma G3 (NEC G3 according to WHO 2010) with primary tumor outside lung
    • Well to moderately differentiated neuroendocrine carcinoma (NET G1/G2) that switched to G3 (confirmed by histology)
    • Neuroendocrine tumor G3 (NET G3)
    E.1.1.1Medical condition in easily understood language
    neuroendocrine cancer
    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 tolerability and safety of everolimus in second-line treatment of poorly differentiated neuroendocrine carcinoma / neuroendocrine carcinoma G3 according to WHO 2010 and neuroendocrine tumors G3. Safety and tolerability of Everolimus can be inferred if type, frequency and seriousness of observed AEs is comparable to those determined in previous Everolimus trials in NET (Radiant-1,2 and 3).
    E.2.2Secondary objectives of the trial
    •To estimate progression free survival (PFS)
    •To estimate Objective Response Rate (ORR)
    •To estimate Disease control rate (DCR)
    •To estimate Duration of Response (DR) and Time to Progression (TTP)
    •To estimate Overall Survival (OS)
    •To evaluate Quality of Life
    •To explore blood levels of tumor markers (chromogranin A & B, neuronspecific enolase, progastrin releasing peptide) as correlative tumor markers for clinical outcome in NET patients
    •To explore expression of mTOR pathway components in tumor tissue (archive) in correlation to tumor response
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed written informed consent
    2. Male or female ≥18 years of age
    3. Patients with poorly differentiated neuroendocrine carcinoma, neuroendocrine carcinoma G3 (NEC – G3 according to WHO 2010) or well or moderately differentiated neuroendocrine carcinoma (NET – G1/ G2) that switched to G3 (confirmed by histology) or neuroendocrine tumor G3 (NET G3) and disease progression as measured by RECIST 1.1
    4. Progression during or after treatment with first-line platin-based chemotherapy. In NET G3 that switched from NET G2 the line of therapy is determined from time of revised histology (confirming a G3 NEN)
    5. Measurable disease according to RECIST 1.1
    6. ECOG status 0-2 (Karnofsky Performance status ≥80%)
    7. Women of child-bearing potential must have a negative pregnancy test
    8. Laboratory requirements:
    • Hematology
    o Absolute neutrophil count ≥1.5x10^9/L
    o Platelet count ≥100x10^9/L
    o Leukocyte count ≥3.0x10^9/L
    o Hemoglobin ≥9 g/dL or 5.59 mmol/l
    • Hepatic Function
    o Total bilirubin ≤1.5 time the upper limit normal (ULN)
    o AST ≤3xULN in absence of liver metastases, or ≤5xULN in presence of liver metastases
    o ALT ≤3xULN in absence of liver metastases, or ≤5xULN in presence of liver metastases
    • Renal Function
    o Creatinine clearance ≥50 mL/min according to Cockroft-Gault formula
    • Metabolic Function
    o Magnesium ≥ lower limit of normal
    o Calcium ≥ lower limit of normal
    o Others:
    o CRP (PCT if CRP is elevated to exclude infection)
    o negative urinary screening test for leucocytes and nitrite to exclude urinary tract infection (U - stix)
    E.4Principal exclusion criteria
    1. Known or suspected allergy or hypersensitivity reaction to any of the components of study treatment or their exipients.
    2. Previous therapy with mTOR inhibitor
    3.Radiotherapy :
    • Concurrent radiotherapy involving target lesions used for this study.
    • Concurrent palliative radiation (but radiation for non-target lesions is allowed if other target lesions are available outside the involved field)
    • previous pre-operative or post-operative radiotherapy within 3 months before study treatment
    4. History of other malignant tumors within the last 5 years, except basal cell carcinoma or curatively excised cervical carcinoma in situ
    5. Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
    6. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤1year before enrolment
    7. Inadequate pulmonary function according to the Investigator’s judgment, history of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
    8. Known active HBV, HCV or HIV infection
    9. Serious concomitant disease or medical condition that in the judgment of the investigator renders the patient at high risk from treatment complication
    10. Any systemic disease requiring oral intake of corticosteroids (except for replacement therapy of corticosteroids – hydrocortisone in case of adrenal or pituitary insufficiency)
    11. Hearing loss ≥ Grade 3 (CTCAE v4.03) 12. Patient pregnant or breast feeding, or planning to become pregnant within 8 weeks after the end of treatment
    13. Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 8 weeks (male or female) after the end of treatment.
    14. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 28 days prior to treatment start
    15. Concurrent treatment with inhibitors (e.g. itraconazol, ketoconazol) and inducers (e.g. phenytoin, rifampicin) of CYP3A4 and/or the multidrug efflux pump P-glycoprotein (PgP).
    16. Known drug abuse/alcohol abuse
    17.Peripheral polyneuropathy ≥ Grade 2 (CTCAE v4.03)
    18. Active chronic inflammatory bowel disease
    19. Any condition which might interfere with study objectives (e.g. infections) or would limit the patient’s ability to complete the study in the opinion of the investigator
    20. Patient who has be incarcerated or involuntarily institutionalized by court order or the authorities (AMG § 40, Abs. 1 No. 4).
    21. Affected persons who might be dependent on the sponsor or the investigator
    E.5 End points
    E.5.1Primary end point(s)
    •Incidence of adverse events (AEs) overall and by severity, and serious adverse events (SAEs).
    E.5.1.1Timepoint(s) of evaluation of this end point
    at study end: Q1/2018
    E.5.2Secondary end point(s)
    •Progression free survival (PFS) as the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse as per local radiology assessment using RECIST 1.1.)
    •Objective response rate defined as the rate of best overall response (CR+PR), determined by RECIST V 1.1.
    •Disease control rate defined as the rate of best overall response and stable disease (CR+PR+SD), determined by RECIST V 1.1.
    •Duration of response is defined as the time from onset of the first objective tumor response (CR/PR) to objective tumor progression or death from any cause. Time to progression (TTP) is the time from date of start of treatment to the date of event defined as the first documented progression due to underlying cancer.
    •OS is defined as the time from date of randomization to the date of death from any cause. If a patient is not known to have died at the date of analysis cut-off, the OS will be censored at the last date of contact.
    •Quality of life (HRQoL) will be evaluated using the EORTC QLQ-C30.
    •Percentage of patients showing normalization or a decrease of chromogranin A & B, neuronspecific enolase, progastrin releasing peptide.
    •To explore expression of mTOR pathway components in tumor tissue (archive) in correlation to tumor response
    E.5.2.1Timepoint(s) of evaluation of this end point
    at study end: Q1/2018
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy No
    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 concerned12
    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
    The planned recruitment of 40 patients will be discontinued when tumor progression has been observed for 28 patients. Patients who are still receiving study treatment at this time can be further treated until progression or an unacceptable toxicity occurs, or for any other reason, which might end the treatment.
    The final statistical analysis will be performed when the last patient has completed at least 3 months of follow-up / the first follow-up visit.
    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 months18
    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.1.3Elderly (>=65 years) Yes
    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 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 state40
    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)
    at the discretion of the local investigator at the patients' site
    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 Decision2015-03-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-11-28
    P. End of Trial
    P.End of Trial StatusCompleted
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