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    The EU Clinical Trials Register currently displays   41467   clinical trials with a EudraCT protocol, of which   6815   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2020-001776-15
    Sponsor's Protocol Code Number:MS202202-0002
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-08-07
    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 ConcernedCzechia - SUKL
    A.2EudraCT number2020-001776-15
    A.3Full title of the trial
    A Phase II single-arm study to investigate tepotinib
    combined with cetuximab in RAS/BRAF wild-type
    left-sided metastatic colorectal cancer (mCRC)
    patients having acquired resistance to anti-EGFR
    antibody targeting therapy due to MET
    amplification
    Jednoramenná studie fáze II k vyhodnocení přípravku tepotinib v kombinaci s cetuximabem u pacientů s levostranným metastazujícím kolorektálním karcinomem s RAS/BRAF divokého typu (mCRC), kteří mají získanou rezistenci vůči cílené terapii proti protilátkám anti-EGFR v důsledku amplifikace MET.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase II single-arm study of tepotinib combined
    with cetuximab
    A.4.1Sponsor's protocol code numberMS202202-0002
    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 SponsorMerck Healthcare KGaA
    B.1.3.4CountryGermany
    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 supportMerck Healthcare KGaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck KGaA
    B.5.2Functional name of contact pointCommunication Center
    B.5.3 Address:
    B.5.3.1Street AddressFrankfurter Str. 250
    B.5.3.2Town/ cityDarmstadt
    B.5.3.3Post code64293
    B.5.3.4CountryGermany
    B.5.4Telephone number+496151725200
    B.5.5Fax number+496151725200
    B.5.6E-mailservice@merckgroup.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 nameTepotinib
    D.3.2Product code MSC2156119J
    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 INNTepotinib
    D.3.9.2Current sponsor codeMSC2156119J
    D.3.9.4EV Substance CodeSUB189535
    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.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 Erbitux
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Europe B.V.
    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 nameCetuximab
    D.3.2Product code MSB0010442D
    D.3.4Pharmaceutical form 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 INNCETUXIMAB
    D.3.9.1CAS number 205923-56-4
    D.3.9.2Current sponsor codeMSB0010442D
    D.3.9.4EV Substance CodeSUB01178MIG
    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 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
    left-sided metastatic colorectal cancer (mCRC)
    E.1.1.1Medical condition in easily understood language
    metastatic colorectal cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal cancer
    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
    Safety Run-in:
    To confirm the recommended Phase II dose (RP2D) of tepotinib when used in combination with cetuximab
    Overall Study:
    To evaluate the preliminary efficacy of tepotinib (RP2D) in combination with cetuximab in terms of tumor response
    E.2.2Secondary objectives of the trial
    Overall Study:
    1) To further evaluate the efficacy of the combination of tepotinib (RP2D) and cetuximab in terms of:
    - a)duration of response (DoR)
    - b) progression-free survival (PFS)
    - c)overall survival (OS)
    2) To evaluate the safety and tolerability of tepotinib in combination with cetuximab
    3) To characterize the immunogenicity of cetuximab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Age
    1. Are ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age) at the time of signing the informed consent.
    Type of Participant and Disease Characteristics
    2. Advanced (locally advanced or metastatic) left sided CRC with RAS/BRAF wild-type at study entry confirmed prior to enrollment, with previous anti-EGFR therapy and acquired resistance on the most recent anti-EGFR monoclonal antibody therapy (panitumumab or cetuximab) by radiological documentation of disease progression according to RECIST Version 1.1.
    3. MET amplification detected by a positive liquid biopsy and/or tissue with appropriate regulatory status (collected after disease progression of the previous anti-EGFR therapy).
    4. Measurable disease by Investigator in accordance with RECIST Version 1.1.
    5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
    6. Life expectancy > 3 months.
    7. Participants having at least one systemic treatment for mCRC including 1 anti-EGFR monoclonal antibody therapy as the most recent line of therapy for mCRC before study treatment and must have shown a radiologically confirmed by RECIST Version 1.1 complete response (CR) or partial response (PR), both for at least 4 months or stable disease (SD) for at least 6 months to that therapy prior to disease progression.
    a. For Cohort A in sites outside of US, participants must only have had one prior systemic treatment for mCRC.
    b. For Cohort B in sites in the US only, participants must have had at least two prior systemic treatments for mCRC.
    8. Less than 2 months between the last administration of the most recent EGFR containing regimen and first dosing in this study.
    9. Adequate hematological function in the absence of transfusions in 7 days before testing defined by white blood cell count ≥ 3 × 109/L with absolute neutrophil count, ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 8.5 g/dL.
    10. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × upper limit of normal (ULN), AST ≤ 3 × ULN, and ALT ≤ 3 × ULN. For participants with liver metastases: total bilirubin ≤ 1.5 × ULN, AST/ALT ≤ 5 × ULN.
    11. Adequate renal function defined by an estimated glomerular filtration rate > 30 mL/min according to the 4-component Modification of Diet in Renal Disease (MDRD) equation. (GFR [mL/min/1.73 m2] = 175 × serum creatinine (Scr)-1.154 × age 0.203 × 1.212 [if African American] × 0.742 [if female]).

    Sex
    12. Are male or female
    Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies.

    Informed Consent
    13. Capable of giving signed informed consent
    E.4Principal exclusion criteria
    Medical Conditions
    1. Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS metastases. Also excluded are participants with carcinomatous meningitis.
    2. Participants who have brain metastasis as the only measurable lesion.
    Prior/Concomitant Therapy
    3. Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer purposes, targeted therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of study intervention, except for the anti-EGFR containing regimen including associated chemotherapy if applicable, which may be continued until enrollment of the participant in the study.
    Prior/Concurrent Clinical Study Experience
    4. Any unresolved toxicity Grade 2 or more according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, from previous anticancer therapy excluding neuropathy, alopecia and rash.
    Other Exclusions
    5. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v 5.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more occurrences of partially controlled asthma).
    6. Discontinuation of the most recent cetuximab or panitumumab containing therapy due to an adverse event.
    7. Prior treatment with other agents targeting the HGF/MET pathway.
    8. Impaired cardiac function:
    a. Left ventricular ejection fraction < 45% defined by echocardiography (a screening assessment not required for participants without a history of congestive heart failure unless
    clinically indicated)
    b. Serious arrhythmia
    c. Unstable angina pectoris
    d. New York Heart Association heart failure Class III and IV
    e. Myocardial infarction within the last 12 months prior to study entry
    f. Symptomatic pericardial effusion
    9. Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg).
    10. Past or current history of neoplasm other than mCRC, except for curatively treated nonmelanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and
    with no evidence of disease for at least 5 years.
    11. Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the test products.
    12. Major surgery within 28 days prior to Day 1 of study intervention.
    13. Known infection with human immunodeficiency virus, or an active infection with hepatitis B or hepatitis C virus.
    14. Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or laboratory abnormalities that might increase the risk associated with study participation at the discretion of Investigators.
    15. IMP use in another study within 3 weeks of the first dose of study intervention.
    E.5 End points
    E.5.1Primary end point(s)
    Safety Run-in:
    Occurrence of dose limiting toxicities (DLTs)

    Overall Study:
    Objective response (OR, confirmed complete response [CR] or partial response [PR]) determined according to RECIST Version 1.1 assessed by the Investigators

    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety Run-In:
    Overall Study: Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15 and subsequently every 4 cycles until study closure or disease progression

    E.5.2Secondary end point(s)
    Overall Study:
    1)
    a) DoR (months) according to RECIST Version 1.1 assessed by the Investigators.
    b) PFS (months) according to RECIST Version 1.1 assessed by the Investigators.
    c) OS (months) assessed by the Investigators.

    2)
    - Occurrence of Adverse Events (AE) and treatment related
    AEs
    - Occurrence of clinically significant changes in vital
    signs, laboratory parameters and 12-lead electrocardiogram (ECG) findings

    3)
    Immunogenicity of cetuximab as measured by antidrug antibody (ADA) assays on Day 1 Cycle 1 and End of Treatment Visit
    E.5.2.1Timepoint(s) of evaluation of this end point
    Survival Follow -Up and End of Treatment Visits
    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 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 Yes
    E.6.13.1Other scope of the trial description
    biomarker research, Immunogenicity Assessments
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA31
    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
    Belgium
    Czech Republic
    France
    Italy
    Russian Federation
    Spain
    Turkey
    United Kingdom
    United States
    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 end of the study is defined as the date when the last participant has completed the last visit in the Survival Follow-up.
    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 months5
    E.8.9.1In the Member State concerned days5
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days9
    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: 44
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 4
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 20
    F.4.2.2In the whole clinical trial 48
    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 Decision2020-10-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-09-09
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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