Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2022-000355-37
    Sponsor's Protocol Code Number:MEC-2022-0373
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-08-09
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2022-000355-37
    A.3Full title of the trial
    Nivolumab during active surveillance after neoadjuvant chemoradiation for esophageal cancer: SANO-3 study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Nivolumab during active surveillance after neoadjuvant chemoradiation for esophageal cancer: SANO-3 study
    A.3.2Name or abbreviated title of the trial where available
    SANO-3 study
    A.4.1Sponsor's protocol code numberMEC-2022-0373
    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 SponsorErasmus MC Cancer Institute
    B.1.3.4CountryNetherlands
    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 supportBristol Myers Squibb
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationErasmus MC Cancer Institute
    B.5.2Functional name of contact pointJessie Huizer
    B.5.3 Address:
    B.5.3.1Street Addressdr. molenwaterplein 40
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3015GD
    B.5.3.4CountryNetherlands
    B.5.6E-mailt.j.huizer@erasmusmc.nl
    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 Opdivo (100mg/10ml)
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    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.3.1Product nameNivolumab
    D.3.2Product code BMS-936558
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous 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
    Operable patients ≥ 18 years of age with locoregionally advanced squamous cell- or
    adenocarcinoma of the esophagus or esophagogastric junction
    E.1.1.1Medical condition in easily understood language
    Operable patients ≥ 18 years of age with locoregionally advanced squamous cell- or
    adenocarcinoma of the esophagus or esophagogastric junction
    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 assess the disease-free survival in patients treated with nivolumab during active surveillance in
    patients who have achieved cCR after nCRT for esophageal and gastroesophageal cancer
    E.2.2Secondary objectives of the trial
     To assess health-related quality of life
     To assess 2-year overall and distant metastases-free survival
     To assess toxicity during and after this treatment
     To assess the proportion of patients with curable disease that go on to need surgery
     To assess complications after nivolumab and surgery.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria
    1. Age ≥18;
    2. Written informed consent and ability to understand the nature of the study and the study-related
    procedures and to comply with them
    3. Histologically proven, resectable adenocarcinoma or squamous cell carcinoma of the
    esophagus or GEJ according to the UICC TNM7 definition. Tumors of the esophagus and
    tumors of which the epicentre is within 5 cm of the GEJ are eligible for inclusion in the trial
    (Type 1 and Type 2 according to Siewert classification of esophagogastric adenocarcinoma
    4. Pre-treatment stage cT2-4aN0-3M0 disease. In case of stage cT4a, the possibility for a curative
    resection has to be explicitly verified by the multidisciplinary tumor board
    5. nCRT (CROSS regimen) completed, i.e. all radiotherapy fractions administered.
    6. Complete clinical response 10-14 weeks after nCRT as determined by endoscopy with
    biopsies, EUS with FNA and PET/CT scanning
    7. No prior cytotoxic chemotherapy other than as part of the neoadjuvant chemoradiation
    (CROSS)
    8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
    9. Adequate cardiac function (cardiac function tests such as echocardiography only necessary in
    symptomatic patients).
    10. Adequate respiratory function (pulmonary function tests only necessary in symptomatic
    patients).
    11. Adequate bone marrow function (White Blood Cells >2x10^9/l; Haemoglobin >6,2mmol/L;
    platelets >100x10^9/l). In the event of transfusions, the last red blood cell transfusion should
    be more than 2 weeks before inclusion.
    12. Adequate renal function (Glomerular Filtration Rate >40 ml/min) or Serum creatinine <=1.5 x
    upper limit of normal (ULN)
    13. Adequate liver function (AST and ALT < 3.0 x ULN; Total bilirubin < 1.5 x ULN (except
    participants with Gilbert Syndrome who may have a total bilirubin level of < 3.0 x ULN)
    14. Women of child-bearing potential must have a negative serum pregnancy test during screening
    period
    15. Patients must be willing to use adequate contraception during the study and for 3 months after
    the end of the study.
    E.4Principal exclusion criteria
    Exclusion criteria
    1. Language difficulty, dementia or altered mental status prohibiting the understanding and giving of
    informed consent and to complete quality of life questionnaires;
    2. Patients who were treated with definitive chemoradiotherapy

    3. Esophageal cancer evaluated as not curatively-resectable by the multidisciplinary tumour board,
    for instance because ingrowth in the trachea, aorta or vertebra (cT4b)
    4. Gastric carcinoma
    5. Clinically significant (active) cardiac disease (e.g. symptomatic coronary artery disease or
    myocardial infarction within last 12 months)

    6 Pregnant and lactating women, or patients of reproductive potential who are not using effective
    birth control methods. If barrier contraceptives are used, they must be continued by both sexes
    throughout the study.
    7 Participation, current or during the last 30 days prior to informed consent, in another intervention
    trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention of this study.
    8. Expected lack of compliance with the protocol
    9. Refusal to undergo further active surveillance (i.e., opting for esophageal resection)
    10. Prior malignancy active within the previous 2 years except for locally curable cancers that have
    been apparently cured or successfully resected, such as basal or squamous cell skin cancer,
    superficial bladder cancer, or GC, or carcinoma in situ of the prostate, cervix, or breast
    11. Participants with an active, known or suspected autoimmune disease. Participants with type I
    diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as
    vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur
    in the absence of an external trigger are permitted to enrol.
    12. Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily
    prednisone equivalents for adults, or > 0.25 mg/kg daily prednisone equivalent for adolescent) or
    other immunosuppressive medications within 14 days of study treatment. Inhaled or topical steroids
    and adrenal replacement doses > 10 mg daily prednisone equivalents for adults, or > 0.25 mg/kg
    daily prednisone equivalent for adolescents are permitted, in the absence of active autoimmune
    disease.
    13. Participants who received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137,
    or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation
    or checkpoint pathways
    14. Anti-tumor treatment other than as part of neoadjuvant chemoradiation (CROSS) within 28 days of
    first administration of study treatment
    15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired
    immunodeficiency syndrome (AIDS).
    16. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g,
    hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV)
    positive (except if HCV-RNA negative)
    17. Participants must not have received a live / attenuated vaccine within 30 days of first treatment.
    18. History of severe hypersensitivity reactions to other monoclonal antibodies
    19. History of allergy or hypersensitivity to study drug components
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoint is disease-free survival (DFS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    defined as the time elapsed between inclusion and
    locoregional or distant disease recurrence or death, whichever comes first.
    E.5.2Secondary end point(s)
    - proportion of patients who develop locoregional disease recurrence
    - proportion of patients who develop distant metastases
    - proportion of patients that undergo esophageal surgery with curative intent
    - Overall survival (OS) calculated from the date of inclusion to death due to any cause. Patients still alive
    at last contact will be censored
    - Quality of life, as measured by quality of life questionnaires: EORTC QLQ-OG25 and EORTC-C30
    - Surgical morbidity (Clavien-Dindo grade 3B or higher) and mortality (30-day and-or in hospital mortality).
    Complications will be monitored according to the Dutch Society for Surgery complication registry (DUCA)
    and Esophagectomy Complications Consensus Group ECCG
    - Serious adverse events and grade 3-4 adverse events from the time of their first treatment with nivolumab
    according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Follow up: at baseline, 3, 6, 12 and 24 months after inclusion, overall survival at 2 years
    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 No
    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 Yes
    E.8.1.7.1Other trial design description
    Multicenter, phase II, non-randomized study
    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 concerned6
    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
    Normal follow up:
    Until disease progression or unacceptable toxicity
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    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: 42
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 No
    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 state74
    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)
    Follow-up within SANO-2 study
    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 Decision2022-08-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-08-29
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 08 00:05:42 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA