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    The EU Clinical Trials Register currently displays   43884   clinical trials with a EudraCT protocol, of which   7296   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:2016-001883-12
    Sponsor's Protocol Code Number:GI1616
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-06-21
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2016-001883-12
    A.3Full title of the trial
    A PROSPECTIVE RANDOMIZED, OPEN-LABEL PHASE 2 STUDY OF IMMUNE CHECKPOINT INHIBITION, NIVOLUMAB WITH OR WITHOUT IPILIMUMAB IN COMBINATION WITH RADIATION THERAPY IN PRETREATED PATIENTS WITH METASTATIC PANCREATIC CANCER OR BILIARY TRACT CANCER
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Immune Checkpoint Inhibition in Combination With Radiation Therapy in Pancreatic or Biliary tract Cancer Patients
    A.3.2Name or abbreviated title of the trial where available
    CheckPAC
    A.4.1Sponsor's protocol code numberGI1616
    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 SponsorHerlev & Gentofte Hospital, Oncology Dept.
    B.1.3.4CountryDenmark
    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 supportOncology dept. Herlev & Gentofte Hospital
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportBristol-Myers Squibb
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportVarian
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationOncology dept. Herlev & Gentofte Hospital
    B.5.2Functional name of contact pointDorte Nielsen
    B.5.3 Address:
    B.5.3.1Street AddressBorgmester Ib Juuls Vej 1
    B.5.3.2Town/ cityHerlev
    B.5.3.3Post code2730
    B.5.3.4CountryDenmark
    B.5.4Telephone number+4538682344
    B.5.5Fax number+4538683570
    B.5.6E-mailDorte.Nielsen.01@regionh.dk
    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®
    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 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 INNNivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.2Current sponsor code1616
    D.3.9.3Other descriptive nameNIVOLUMAB
    D.3.9.4EV Substance CodeSUB122750
    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.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 Yervoy®
    D.2.1.1.2Name of the Marketing Authorisation holderBristol–Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationDenmark
    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 nameipilimumab
    D.3.4Pharmaceutical form Concentrate for solution for 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 INNIPILIMUMAB
    D.3.9.1CAS number 477202-00-9
    D.3.9.2Current sponsor code1616
    D.3.9.3Other descriptive nameBMS734016
    D.3.9.4EV Substance CodeSUB29397
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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
    Patients with metastatic pancreatic cancer or metastatic biliary tract cancer
    E.1.1.1Medical condition in easily understood language
    Patients with metastatic pancreatic cancer or metastatic biliary tract cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10033605
    E.1.2Term Pancreatic cancer metastatic
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10077846
    E.1.2Term Cholangiocarcinoma metastatic
    E.1.2System Organ Class 100000004864
    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 clinical benefit rate of immune checkpoint inhibition,ipilimumab and/or nivolumab in combination with RT
    E.2.2Secondary objectives of the trial
    To study the safety, tolerability, feasibility , effectiveness and quality of life of ipilimumab and/or nivolumab in combination with RT
    To estimate overall survival probability after 6 months and at 1 year in the each arm
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    8.3 SUBJECT INCLUSION CRITERIA
    Patients with:
    • Signed informed consent
    o Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care
    o Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
    • Histopathological confirmation of pancreatic adenocarcinoma or biliary tract cancer prior to entering this study OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are consistent with a diagnosis of PC or biliary tract cancer
    • At least one measurable primary in-situ (or locally-recurrent) or metastatic tumor must be present and, in the opinion of radiation oncologist, be amenable to RT as planned in the protocol and at least one additional metastatic tumor that will not undergo RT and which is measurable according to RECIST 1.1 criteria. Both lesions must be accessible for image-guided percutaneous biopsy
    • There is no upper limit on the number of prior chemotherapy regimens received. Patients must have received and failed or intolerance to at least one line of prior systemic chemotherapy with gemcitabine or platinum-containing regimens for unresectable and/or metastatic PC or BTC
    • Age > 18 years and older
    • Life expectancy greater than 3 months
    • ECOG/WHO Performance Status (PS) 0-1
    • Patients must have normal organ and marrow function as defined below:
    o White blood cell count (WBC) ≥ 2 x 10⁹/L
    o Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
    o Hemoglobin ≥ 5,6 mmol/l
    o Platelet count ≥ 100 x 10⁹/L
    o Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin < 3.0 mg/dL)
    o ASAT/ALAT ≤ 3 x ULN ( < 5 x ULN if known liver metastasis)
    o PP ≥ 40 or INR ≤ 1.5
    o Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 40 mL/min (using the Cockcroft-Gault formula)
    • Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated in Appendix 27.10. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception and duration should be determined in consultation with the investigator. WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. WOCBP should therefore use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
    • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab
    • Women must not be breastfeeding
    • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (Appendix 27.10). The investigator shall review contraception methods and the time period that contraception must be followed. Men that are sexually active with WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. Men who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception
    • Subjects with PC must have signed and dated a BIOPAC and patients with BTC must have signed and dated a CHOCA approved written informed consent form in accordance with regulatory and institutional guidelines.
    E.4Principal exclusion criteria
    8.4 SUBJECT EXCLUSION CRITERIA
    Patients with:
    • Malignant ascites that is clinically detectable by physical examination or is symptomatic. Evidence of radiographic ascites that is not clinically significant will not be exclusion criteria
    • 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
    • No chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study
    • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
    • Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
    • Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
    • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
    • As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab and ipilimumab-containing regimen
    • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    • Allergies and Adverse Drug Reaction
    o History of allergy to study drug components
    o History of severe hypersensitivity reaction to any monoclonal antibody
    • WOCBP who are pregnant or breastfeeding
    • Women with a positive pregnancy test at enrollment or prior to administration of study medication
    • Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
    E.5 End points
    E.5.1Primary end point(s)
    Clinical benefit rate (CBR), (CBR = stable disease (SD) or partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Time Frame: Approximately up to 6 months.
    E.5.2Secondary end point(s)
    • Safety (Data on safety parameters). Safety and tolerability of nivolumab with or without ipilimumab in combination with radiation therapy assessed by a summary of adverse events and clinical laboratory assessments
    • CBR according to modified immune-related Response Criteria (irRC) (Appendix 27.5)
    • Overall response rate (ORR), (ORR = PR or CR) according to RECIST 1.1 and modified irRC
    • Progression free survival (PFS), defined as the time from the date of randomization until the date of PD determined by investigator assessment of objective radiographic disease assessments per RECIST 1.1 and modified irRC, or death due to any cause if sooner
    • Overall survival (OS) rate at 6 months and at 1 year. The Kaplan-Meier estimate of proportion of patients that survived from the date of randomization by 6 months and at 1 year
    • OS, defined as the time from the date of randomization until death due to any cause
    • Quality of Life (Quality of Life Questionnaire C30 (QLQ-C30) Version 3.0)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Time Frame: Approximately up to 6 months and 1 year.
    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 Yes
    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 Yes
    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) Yes
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days0
    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: 53
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 87
    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 state140
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 140
    F.4.2.2In the whole clinical trial 140
    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)
    other types of chemotherapy and /or best supporttive care according to local guidelines
    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 Decision2016-08-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-09-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-11-09
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