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    Summary
    EudraCT Number:2018-003011-22
    Sponsor's Protocol Code Number:ETOP_14-18
    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:2019-11-12
    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 number2018-003011-22
    A.3Full title of the trial
    A multicentre single arm phase II trial assessing the efficacy of immunotherapy, chemotherapy and stereotactic radiotherapy to metastases followed by definitive surgery or radiotherapy to the primary tumour, in patients with synchronous oligo-metastatic non-small cell lung cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II trial assessing the efficacy (how well the treatment works), safety and tolerability (side effects of treatment) of the antibody drug durvalumab, administered together with tremelimumab, standard chemotherapy and radiotherapy
    A.3.2Name or abbreviated title of the trial where available
    CHESS
    A.4.1Sponsor's protocol code numberETOP_14-18
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03965468
    A.5.4Other Identifiers
    Name:AstraZeneca Number:Number:ESR-17-13224
    Name:AstraZeneca D-code:Number:D4191C00092
    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 SponsorETOP IBCSG Partners Foundation
    B.1.3.4CountrySwitzerland
    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 supportAstraZeneca
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationETOP IBCSG Partners Foundation
    B.5.2Functional name of contact pointCoordinating Center
    B.5.3 Address:
    B.5.3.1Street AddressEffingerstrasse 33
    B.5.3.2Town/ cityBern
    B.5.3.3Post code3008
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number413131 511 94 00
    B.5.5Fax number413131 511 94 01
    B.5.6E-mailCHESS@etop.ibcsg.org
    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 namedurvalumab
    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 INNDURVALUMAB
    D.3.9.1CAS number 1428935-60-7
    D.3.9.2Current sponsor codeMEDI4736
    D.3.9.4EV Substance CodeSUB176342
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Yes
    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 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 nameTremelimumab
    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 INNTremelimumab
    D.3.9.1CAS number 745013-59-6
    D.3.9.4EV Substance CodeSUB37101
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Yes
    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
    Synchronous oligo-metastatic Non-Small Cell Lung Cancer (NSCLC)
    E.1.1.1Medical condition in easily understood language
    a type of lung cancer that is called Non-Small Cell Lung Cancer (NSCLC) that spread in some parts of the body (oligo-metastatic)
    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 PT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    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 evaluate PFS in synchronous oligometastatic NSCLC patients treated with induction immunotherapy, chemotherapy and stereotactic body radiation therapy (SBRT) to all metastases followed by definitive surgery or radiotherapy to the locoregional primary tumour .
    E.2.2Secondary objectives of the trial
    1) To evaluate secondary measures of clinical efficacy including progression-free survival, overall survival, pattern of disease progression, response to induction therapy, overall response and duration of response.
    2) To assess the safety and tolerability of the treatment.
    3) To evaluate symptom-specific and global quality of life.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Histological confirmed NSCLC
    - Measurable disease as assessed by RECIST v1.1
    - Synchronous oligo-metastatic stage IV disease:
    - max 3 distant metastases, one of which must be extra-cerebral for SBRT
    - Initial mediastinal staging is recommended (except for lymph nodes <1cm on CT and PET-negative) preferably by endobronchial ultrasound (EBUS)
    - Neurosurgical resection of one single CNS metastasis or laparoscopic resection of one adrenal metastasis before study inclusion is
    allowed (one extra-cerebral metastass must be available for SBRT)
    - Able to understand and give written informed consent and comply with study procedures
    - Age ≥18 years
    - Body weight >30kg
    - ECOG Performance Status 0-1
    - Availability of tumour tissue for translational research
    - Adequate haematological, renal and liver function
    - Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before enrolment.
    - Life expectancy of ≥12 weeks
    - Written IC for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention.
    E.4Principal exclusion criteria
    - Prior chemotherapy, radiotherapy or therapeutical surgery for NSCLC (an exception is the resection of one single CNS or adrenal metastasis)
    - Activating driver mutation: EGFR, ALK, ROS1
    - >3 distant metastases
    - Brain metastases not amendable for radiosurgery or neurosurgery
    - Extracranial metastatic locations such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiomatosis of skin or lung, diffuse bone marrow metastasis, abdominal masses/abdominal organomegaly, identified by physical examination that is not measurable by reproducible imaging techniques.
    - Primary lung cancer not suitable for radical therapy (pneumonectomy excluded)
    - History of leptomeningeal carcinomatosis
    - Major surgery or significant traumatic injury from which the patient has not recovered at least 28 days before enrolment
    - Any unresolved toxicities (grade ≥2) from previous anticancer therapy other than for NSCLC, with the exception of alopecia or vitiligo, and the laboratory values defined in the inclusion criteria:
    - Patients with grade ≥2 neutropathy will be evaluated on a case-by-case basis after consultation with the ETOP Medical Affairs team.
    - Patients with irreversible toxicity not reasonable expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with ETOP Medical Affairs team.
    - Any uncontrolled intercurrent illness, including but not limited to: ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease or serious chronic gastrointestinal conditions associated with diarrhoea, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol.
    - Known active hepatitis infection , positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc) at screening.
    - Known positivity for human immunodeficiency virus (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).
    - Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment (including inflammatory bowel disease [e.g., colitis or Crohn's disease ], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis Syndrome, or Wegener Syndrome [granulomatosis with polyangiitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]. The following are exceptions to this criterion:
    - Patients with vitiligo or alopecia
    - Patient with hypothyroidism (e.g. , following Hashimoto syndrome) stable on hormone replacement
    - Any chronic skin conditions that does not require systemic therapy
    - Patients without active disease in the last five years may be included but only after consultation with the study physician
    - Patient with celiac disease controlled by diet alone
    - Active malignancy requiring concurrent intervention
    - Severe or uncontrolled cardiac disease requiring treatment
    - History of active primary immunodeficiency
    - History of allogeneic organ transplant
    - Receipt of live attenuated vaccines within 30 days prior to enrolment
    - Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab and tremelimumab, with the exception of the following:
    - Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
    - Systemic corticosteroids at physiologic doses not to exceet 10 mg per day of prednisone or its equivalent
    - Steroids as premedicatin for hypersensitivity reactions (e.g., CT scan premedication)
    - Known allergies or hypersensitivity to trial drugs or to any excipient.
    - Woman who are pregnant or in the period of lactation.
    - Sexually active men and women of childbearing potential who are not willing to use a highly effective contraceptive method during the trial and for up to 90 days after last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab and tremelimumab combination therapy.
    E.5 End points
    E.5.1Primary end point(s)
    Progression-free survival (PFS) at 12 months
    E.5.1.1Timepoint(s) of evaluation of this end point
    after 12 months (±2 weeks) from start of combined durvalumab and tremelimumab treatment.
    E.5.2Secondary end point(s)
    1) Overall survival (OS)
    2) Pattern of disease progression
    3) Response to induction therapy
    4) Distant progression-free survival
    5) Overall response (OR)
    6) Duration of response (DOR)
    7) Symptom-specific and global quality of life
    8) Toxicity before and after surgery/radiotherapy
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) from enrolment date until death from any cause. Censoring occurs at the last follow-up date.
    2) site of first progression evaluated up to one year after enrollment.
    3) best overal response evaluated from start of treatment until end of induction phase (restaging at 3-month)
    4) development of new metastases across all timepoints
    5) from start of treatment across all time points until treatment discontinuation
    6) from date of first objective response to date of first progression or relapse
    7) at baseline; 3 weeks and 3 months after treatment start (at the time point of restaging). For patients without disease progression at restaging: before definitive local treatment and 6, 9 and 12 months after treatment start
    8) from date enrolment until 90 days after treatment discontinuation
    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 Yes
    E.8.1.7.1Other trial design description
    single-arm
    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.8.3 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Switzerland
    Netherlands
    Spain
    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
    database lock (90 days after 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 months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    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: 55
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 41
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 54
    F.4.2.2In the whole clinical trial 96
    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)
    none
    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 Decision2019-11-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-20
    P. End of Trial
    P.End of Trial StatusOngoing
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