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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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:2013-005532-23
    Sponsor's Protocol Code Number:CO-1686-019
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-11-06
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2013-005532-23
    A.3Full title of the trial
    TIGER-2: A Phase 2, Open-Label, Multicenter, Safety and Efficacy Study of Oral CO 1686 as 2nd Line EGFR-Directed TKI in Patients with Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 clinical study to evaluate the safety and efficacy of the study medication CO-1686 in subjects with Previously Treated EGFR Non-Small Cell Lung Cancer
    A.3.2Name or abbreviated title of the trial where available
    TIGER-2
    A.4.1Sponsor's protocol code numberCO-1686-019
    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 SponsorClovis Oncology, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportClovis Oncology, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClovis Oncology UK Ltd
    B.5.2Functional name of contact pointDr Lindsey Rolfe
    B.5.3 Address:
    B.5.3.1Street AddressSheraton House, Castle Park
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeCB3 0AX
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+441223370037
    B.5.6E-mailinfo@clovisoncology.com
    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 nameCO-1686
    D.3.2Product code CO-1686
    D.3.4Pharmaceutical form Film-coated 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.3.8INN - Proposed INNNot applicable
    D.3.9.1CAS number 1446700-26-0
    D.3.9.2Current sponsor codeCO-1686
    D.3.9.3Other descriptive nameCO-1686
    D.3.9.4EV Substance CodeSUB126980
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    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 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 nameCO-1686
    D.3.2Product code CO-1686
    D.3.4Pharmaceutical form Film-coated 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.3.8INN - Proposed INNNot applicable
    D.3.9.1CAS number 1446700-26-0
    D.3.9.2Current sponsor codeCO-1686
    D.3.9.3Other descriptive nameCO-1686
    D.3.9.4EV Substance CodeSUB126980
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    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
    Previously treated NSCLC patients who have documented evidence of an
    activating mutation in the EGFR gene and have failed treatment with an
    EGFR inhibitor
    E.1.1.1Medical condition in easily understood language
    Patients with EGFR mutant Non-Small Cell Lung Cancer who have failed
    treatment with an EGFR inhibitor
    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 LLT
    E.1.2Classification code 10029514
    E.1.2Term Non-small cell lung cancer NOS
    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 antitumor efficacy of PO single agent CO 1686, as measured by ORR, when administered to patients with EGFR mutated, centrally confirmed T790M positive and T790M negative advanced NSCLC after tumor progression on 1 previous EGFR directed TKI
    E.2.2Secondary objectives of the trial
    •To assess clinical efficacy in patients with centrally confirmed T790M positive NSCLC: disease control rate (DCR), duration of response (DR), PFS, and OS following CO 1686 treatment
    •To assess quality of life (QoL) by patient reported outcomes (PRO) following CO 1686 treatment
    •To evaluate the safety and tolerability of CO 1686
    •To determine the pharmacokinetics (PK) of CO 1686 using POPPK methods and explore correlations between PK, exposure, response, and/or safety findings
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Except where specified, inclusion criteria are applicable to both Cohorts A and B of the study.
    1. Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC
    2. Documented evidence of a tumor with 1 or more EGFR mutations excluding exon 20 insertion
    •Disease progression confirmed by radiologic assessment while receiving treatment with the first single agent EGFR TKI (eg, erlotinib, gefitinib, afatinib, or dacomitinib)
    o EGFR TKI treatment discontinued ≤ 30 days prior to planned initiation of CO 1686 (the washout period for an EGFR inhibitor is a minimum of 3 days)
    o No intervening treatment between cessation of single agent EGFR TKI and planned initiation of CO 1686
    o Previous treatment with ≤ 1 prior chemotherapy (excluding prior neo adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent)
    o Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less
    • Central laboratory confirmation of the presence of the T790M mutation in tumor tissue in Cohort A and the presence or absence of the T790M mutation in tumor tissue in Cohort B. Centrally indeterminate, unknown or invalid specimens are not acceptable. Biopsy material obtained from either primary or metastatic tumor tissue must have been obtained (and sent to the central laboratory) within 60 days prior to dosing study drug but following disease progression on the first EGFR TKI.
    3. Measureable disease according to RECIST Version 1.1
    4. Life expectancy of at least 3 months
    5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
    6. Age ≥ 18 years (in certain territories, the minimum age requirement may be higher, eg age ≥ 20 years in Japan and Taiwan)
    7. Adequate hematological and biological function, confirmed by the following laboratory values:
    • Bone Marrow Function
    o Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
    o Platelets > 100.0 × 10^9/L
    o Hemoglobin ≥ 9 g/dL (or 5.6 mmol/L)
    • Hepatic Function
    o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); if liver metastases, ≤ 5 × ULN
    o Bilirubin ≤ 2 × ULN
    • Renal Function
    o Serum creatinine ≤ 1.5 × ULN
    • Electrolytes
    oPotassium and magnesium within normal range. Patients may receive supplements to meet this requirement
    8. Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved ICF prior to any study specific evaluation
    E.4Principal exclusion criteria
    Except where specified, exclusion criteria are applicable to both Cohorts A and B of the study.
    1. Documented evidence of an exon 20 insertion activating mutation in the EGFR gene
    2. Active second malignancy; i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
    • Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior
    3. Known pre existing interstitial lung disease
    4. Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 4 weeks prior to the start of study treatment). Cohort B only: Patients with CNS metastases or leptomeningeal carcinomatosis are excluded.
    5. Treatment with prohibited medications (eg, concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment [except corticosteroids and megesterol acetate], or immunotherapy) ≤ 14 days prior to treatment with CO 1686
    6. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting CO 1686
    • see http://crediblemeds.org/ for a list of QT prolonging medications (includes all medication under categories of Known, Possible and Conditional risk of Torsades de Pointes)
    7.Prior treatment with CO 1686, or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR eg, AZD9291, HM61713, TAS 121
    8. Any of the following cardiac abnormalities or history:
    • Clinically significant abnormal 12 lead ECG, QT interval corrected using Fridericia’s method (QTCF) > 450 msec
    • Inability to measure QT interval on ECG
    • Personal or family history of long QT syndrome
    • Implantable pacemaker or implantable cardioverter defibrillator
    • Resting bradycardia < 55 beats/min
    9. Nonstudy related surgical procedures ≤ 7 days prior to administration of CO 1686. In all cases, the patient must be sufficiently recovered and stable before treatment administration
    10. Females who are pregnant or breastfeeding
    11. Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 12 weeks after the last dose of CO 1686
    12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
    13. Any other reason the investigator considers the patient should not participate in the study
    E.5 End points
    E.5.1Primary end point(s)
    ORR according to RECIST Version 1.1. For Cohort A, ORR will undergo independent radiology review (IRR) and in Cohort B, scans will be assessed by IRR if needed as a supporting analysis.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The ORR is the best overall response recorded from the start of the treatment until disease progression or recurrence.
    E.5.2Secondary end point(s)
    • DR, DCR and PFS according to RECIST Version 1.1 as determined by IRR
    • ORR, DR, DCR and PFS according to RECIST Version 1.1 as determined by Investigator Assessment
    • OS
    • Change from baseline in patient reported outcomes using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C30), EORTC Quality of Life Questionnaire Lung Cancer module (EORTC QLQ LC13), and the Dermatology Life Quality Index (DLQI)
    • Treatment emergent adverse events (AEs), laboratory abnormalities and ECG abnormalities
    • Plasma PK parameters for CO-1686 based on sparse sampling
    E.5.2.1Timepoint(s) of evaluation of this end point
    From start of treatment until disease progression
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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, open label, dual cohort clinical trial
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 EEA38
    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
    Australia
    Canada
    France
    Germany
    Hong Kong
    Korea, Republic of
    Netherlands
    Spain
    Switzerland
    Taiwan
    United Kingdom
    United States
    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
    Once study treatment has been discontinued and the End of Treatment visit has been completed, study participation will cease. Investigational centers will interpret tumor scans locally for the purpose of making treatment decisions and for final tumor response evaluation. The study will close once all patients have either completed participation, have transferred to a locally approved treatment access program in accordance with relevant local regulations or the sponsor decides to close the study.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months1
    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: 81
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 144
    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 state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 65
    F.4.2.2In the whole clinical trial 225
    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)
    After the end of treatment the patients will return to their normal SOC
    medication.
    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 Decision2014-11-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-01-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-08-27
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