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    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7293   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2020-002605-25
    Sponsor's Protocol Code Number:AIO-HEP-0120
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2020-11-09
    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 - PEI
    A.2EudraCT number2020-002605-25
    A.3Full title of the trial
    Neoadjuvant Bintrafusp alfa in patients with resectable biliary tract cancer (NEOBIL)
    Neoadjuvante Therapie mit Bintrafusp alfa bei Patienten mit operablem Krebs der Gallenwege (NEOBIL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Neoadjuvant Bintrafusp alfa in patients with resectable biliary tract cancer (NEOBIL)
    Neoadjuvante Therapie mit Bintrafusp alfa bei Patienten mit operablem Krebs der Gallenwege
    A.3.2Name or abbreviated title of the trial where available
    NEOBIL
    A.4.1Sponsor's protocol code numberAIO-HEP-0120
    A.5.4Other Identifiers
    Name:Merck Healthcare KGaANumber:MS200647_0075
    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 supportMerck Healthcare KGaA
    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 pointAIO-Studien-gGmbH
    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 number004930814534431
    B.5.5Fax number004930322932926
    B.5.6E-mailaio.regulatory@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 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 nameBintrafusp Alfa
    D.3.2Product code MSB0011359C
    D.3.4Pharmaceutical form Infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBINTRAFUSP ALFA
    D.3.9.3Other descriptive nameM7824)
    D.3.9.4EV Substance CodeSUB193581
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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
    Treatment-naive subjects with a diagnosis of resectable biliary tract cancer, confirmed by histopathology
    Behandlungsnaive Patienten mit histologisch diagnostiziertem operablen Gallengangskarzinom
    E.1.1.1Medical condition in easily understood language
    Subjects with a diagnosis of resectable biliary tract cancer, confirmed by histopathology
    Patienten mit der Diagnose eines operablem Gallengangkrebs
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10004593
    E.1.2Term Bile duct cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10004597
    E.1.2Term Bile duct cancer resectable
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10004598
    E.1.2Term Bile duct carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10007289
    E.1.2Term Carcinoma bile duct
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10004601
    E.1.2Term Bile duct carcinoma resectable
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To explore the efficacy of preoperative Bintrafusp alfa (M7824, MSB0011359C) in inducing a major pathological response in biliary tract cancer patients.
    Untersuchung der Wirksamkeit einer präoperativem Behandlung mit Bintrafusp alfa (M7824, MSB0011359C) in Bezug auf die pathologisch gemessene Remission bei Patienten mit Gallengangskarzinom.
    E.2.2Secondary objectives of the trial
    include exploratory objectives namely accumulation of further feasibility data (i.e. safety data, additional efficacy data) as well as a translational research part investigating changes in a subjects’ immune activation determined by blood tests and tissue analysis before and after treatment with Bintrafusp alfa
    Zu den sekundären Zielen gehören explorative Ziele, wie weitere Durchführbarkeitsdaten (z.B. Sicherheitsdaten, zusätzliche Wirksamkeitsdaten) sowie ein translationaler Forschungsteil, der Veränderungen in der Immunaktivität der Patienten untersucht. Hierfür werden Blutuntersuchungen und Gewebeanalysen vor und nach der Behandlung mit Bintrafusp alfa durchgeführt.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent granted prior to initiation of any study-specific screening procedures
    2. Biliary tract cancer, confirmed by histopathology, cytopathology is not sufficient
    3. Resectable disease limited to the liver assessed by an interdisciplinary tumor board involving a hepatobiliary surgeon; No prior systemic therapy.
    4. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and xaminations including follow up.
    5. Age ≥ 18 years
    6. Performance status ECOG 0-1
    7. Normal organ and bone marrow function defined as:
    - Hematopoetic: absolute neutrophil count ≥1,500/mm3, platelet count ≥ 100,000/mm3,
    - hemoglobin ≥9 g/dL
    - normal international normalized ratio (INR), PT ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
    - Hepatic: AST ≤5 x ULN, ALT ≤ 5 x ULN, and bilirubin ≤ 3.0 x ULN.
    - Renal: Creatinine level ≤1.5 x ULN or estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
    8. Special medical conditions and comorbidities:
    - Maximum Child Pugh stage A in patients with cirrhosis
    - HIV: stable on ART for at least 4 weeks, no documented evidence of multi-drug resistance, viral load of < 400 copies/mL and CD4+ T-cells ≥ 350 cells/μL.
    - HBV infection: participant on a stable dose of antiviral therapy, HBV viral load below the limit of quantification.
    9. Women of childbearing potential must have a negative serum or highly sensitive urine pregnancy test performed within 7 days prior to the first dose of IMP
    10. Women of childbearing potential (WOCBP) must use HIGHLY EFFECTIVE method(s) of contraception to avoid pregnancy for the duration of study treatment and further 2 months after the last dose of IMP.
    11. Male participants who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception or to abstain from sexual activity and will be instructed to adhere to either method from the time of first dose until 125 days after the last dose of investigational product. In addition, male subjects must be willing to refrain from sperm donation during this time. Azoospermic men do not require contraception.
    E.4Principal exclusion criteria
    1. Metastatic disease
    2. Prior surgery, systemic therapy, radiation therapy, chemoradiation, transarterial chemoembolisation (TACE), Radiofrequency ablation (RFA) or selective intraarterial Radiotherapy (SIRT) for treatment of CCA. NOTE: Laparoscopy for diagnostic procedures is allowed.
    3. Drug or alcohol addiction, medical or psychological condition that may interfere with the patient´s participation in the study
    4. Participation in another clinical trial with any investigational study drug (whatever the use, curative, prophylactic or diagnostic intent) within 30 days prior to enrollment
    5. Pregnancy or breast feeding women
    6. Regulatory and ethical criteria:
    - Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities [§ 40 Abs. 1 S. 3 Nr. 4 AMG].
    - Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
    7. IMMUNOSUPRESSANTS: “Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or
    equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).”
    8. AUTOIMMUNE DISEASE: “Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.”
    9. PREVIOUS MALIGNANT DISEASE: within the last 3 years except for a. superficial/noninvasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected GI cancers limited to the mucosal layer without recurrence in > 1 year.
    10. INFECTIONS: “Active infection requiring systemic therapy. “
    11. VACCINATION: has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted.
    12. HYPERSENSITIIVTY TO BINTRAFUSP ALFA: “Known severe hypersensitivity [Grade ≥ 3 NCI CTCAE 5.0]) to investigational product bintrafusp alfa or any component in its formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma.
    13. CARDIOVASCULAR DISEASE: “Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.”
    14. BLEEDING: “history of bleeding diathesis or recent major bleeding events (i.e. Grade ≥ 2 bleeding events in the month prior treatment)
    15. Other severe acute or chronic medical conditions: “including drug-induced interstitial lung disease (ILD) or participant has had a history of drug-induced pneumonitis that has requiredoral or IV steroids”, and/or other diseases, which in the opinion of the Investigator might impair the participant’s tolerance for the study or ability to consistently participate in study procedures.
    16. Uncontrolled diabetes as defined by HbA1c > 10.0 %.
    E.5 End points
    E.5.1Primary end point(s)
    Major Pathologic Response measured in the surgically resected tumor
    Major Pathologic Response (MPR) gemessen im resezierten Tumor
    E.5.1.1Timepoint(s) of evaluation of this end point
    after approx. 24 months
    nach ca. 24 Monaten
    E.5.2Secondary end point(s)
    - Tumor response according to RECIST1.1
    - Rate of resectability
    - Adverse events according to CTCAE V5
    - Adverse events of special interest (postoperative wound infections, impaired wound healing, wound dehiscence, prolongation of post-op hospitalization beyond 14 days)
    - Tumoransprechrate nach RECIST1.1 und iRECIST
    - Resektabilitätsrate
    - Unerwünschte Ereignisse gemäß CTCAE V5
    - Unerwünschte Ereignisse von besonderem Interesse (postoperative Wundinfektionen, beeinträchtigte Wundheilung, Wunddehiszenz, Verlängerung des postoperativen Krankenhausaufenthaltes über 14 Tage hinaus)
    E.5.2.1Timepoint(s) of evaluation of this end point
    after approx. 24 months
    nach ca. 24 Monaten
    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 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 concerned10
    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
    The study will be terminated as soon as the last patient has completed 90 days of post-surgery follow-up.
    Das Ende der Studie ist definiert als der Zeitpunkt, an dem der letzte Patient die FU-Visite 90 Tage nach der Operation erhalten hat.
    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 months24
    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: 12
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 12
    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 state24
    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)
    Patients will be treated according to standard-of-care at the discretion of the investigator
    Patienten werden gemäß dem aktuellen Behandlungsstandard nach Ermessen des Arztes behandelt
    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 Decision2021-03-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-03-24
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-01-05
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