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   44236   clinical trials with a EudraCT protocol, of which   7337   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:2004-004849-18
    Sponsor's Protocol Code Number:EMD121974-010
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-07-13
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2004-004849-18
    A.3Full title of the trial
    Cilengitide (EMD121974) and temozolomide with concomitant radiation therapy, followed by cilengitide and temozolomide maintenance therapy in subjects with newly diagnosed glioblastoma multiforme – a multicenter, open-label, uncontrolled Phase I/IIa study
    A.4.1Sponsor's protocol code numberEMD121974-010
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck 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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Information not present in EudraCT
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/03/184
    D.3 Description of the IMP
    D.3.1Product nameCilengitide
    D.3.2Product code EMD121974
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNCilengitide
    D.3.9.1CAS number 188968-51-6
    D.3.9.2Current sponsor codeEMD121974
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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
    Newly diagnosed Glioblastoma (Astrocytoma, WHO grade IV)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 7.1
    E.1.2Level LLT
    E.1.2Classification code 10018336
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this exploratory study is to estimate the percentage of subjects who survived 6 months without disease progression (6-month PFS).
    E.2.2Secondary objectives of the trial
    The secondary objectives are to:
    · Investigate safety and tolerability.
    · Investigate the PK of cilengitide and TMZ.
    · Estimate response rate.
    · Estimate overall survival time.
    · Estimate rate of 1-year survival.
    · Estimate median time to disease progression.

    Additional goals of the study are:
    · To increase the safety database in a well defined population of GB subjects (in
    support of the results from the NABTT-9911 study).
    · To investigate the relationship between efficacy and alterations in molecular profiles
    in order to identify molecular markers that correlate with response or resistance.
    · To measure subject Quality of Life (QoL) by the EORTC- QLQC30 + QLQ BN 20
    and the Functional Assessment of Cancer Therapy–Brain (FACT-Br) 1997.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    - Written informed consent obtained before undergoing any study-related activities
    - Males or females ≥ 18 to < 70 years of age.
    - Newly diagnosed, histologically proven supratentorial GB (WHO Grade IV). The histological diagnosis can be obtained either from a brain biopsy or from a neurosurgical resection of the tumor.
    - Interval of ≥ 3 weeks but ≤ 5 weeks since surgery or biopsy before enrollment.
    - For subjects who had undergone a tumor biopsy, disease evaluated by Gd-MRI within 1 week prior to the first dose of cilengitide.
    - For subjects who had undergone tumor resection or debulking, availability of a postoperative Gd-MRI performed within < 48 hours after surgery. (In the exceptional case that it was not possible to obtain a Gd-MRI within 48 hours post surgery, and upon receiving confirmation from the central registration desk, a Gd-MRI is to be performed within 1 week prior to the start of cilengitide treatment.)
    - Tumor tissue specimens from the GB surgery (paraffin-embedded and fresh-frozen) or biopsy (paraffin-embedded and, if available, fresh frozen) must be available for central pathology review and analysis of molecular markers relevant for this study (avb3 and avb5 integrins and MGMT gene methylation status).
    - No prior chemotherapy in the last 5 years.
    - No prior RT of the head.
    - Stable or decreasing dose of steroids for ≥ 8 days.
    - Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.
    - Women of childbearing potential must have a negative pregnancy test at screening.
    - Subjects with the potential for pregnancy or impregnating their partner must agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar (IUP) or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study drug.
    - Laboratory values (within 1 week prior to the first dose of cilengitide):
    Absolute neutrophil count ≥1500/mm³.
    Platelets ≥ 100,000/mm³.
    Creatinine ≤ 1.5 times upper limit of normal (ULN) or creatine clearance rate ≥ 60 mL/min.
    PT international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits.
    Hemoglobin ≥10 mg/dL.
    Total bilirubin ≤ 1.5 times the ULN.
    Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times above ULN.
    Alkaline phosphatase ≤ 2.5 times above ULN.
    - Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG) measured during screening. No history of stroke.
    E.4Principal exclusion criteria
    - Planned surgery for other diseases (e. g., dental extraction).
    - History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
    - History of prior malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥ 5 years are eligible for this study.
    - History of coagulation disorder associated with bleeding or recurrent thrombotic events.
    - Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
    - Subject is pregnant, anticipates becoming pregnant within 6 months after study participation, or is currently breast-feeding.
    - Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide.
    - Prior antiangiogenic therapy.
    - Placement of Gliadel® wafer at surgery.
    - Unable to undergo Gd-MRI.
    - Current alcohol dependence or drug abuse.
    - Treatment with a prohibited concomitant medication (see Section 6.9.1).
    - Known hypersensitivity to the study treatment.
    - Legal incapacity or limited legal capacity.
    - Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before enrollment in the trial.
    E.5 End points
    E.5.1Primary end point(s)
    The purpose of the current Phase I/IIa study is to investigate the tolerability and activity of the combination of cilengitide with the newly established treatment regimen (RT and TMZ, followed by maintenance TMZ). The current study is an exploratory, uncontrolled, open-label study, the results of which will be compared to the recently published data of the EORTC Phase III study.
    The primary endpoint is the rate of subjects alive and progression-free at 6 months (6-month PFS).
    In the EORTC trial the improvement of PFS correlated with the improvement in overall survival. Therefore this surrogate marker appears to be appropriate for a Phase I/II study. The evaluation of disease progression will be based on radiological and neurological criteria as well as steroid use.
    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 Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic Yes
    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 Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    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.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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 clinical study will be the last visit of the last subject after the last cilengitide administration (end of the Continuing Treatment Phase).
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-07-13. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 50
    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)
    Subjects who, after completing 35 weeks of treatment, are without progression will be offered the opportunity, in agreement with the responsible investigator, to continue therapy beyond Week 35 as long as it may be of benefit to the subject. Cilengitide administration will continue until progression or the occurrence of unacceptable AEs or the subject has remained stable long enough that the investigator considers it unnecessary to continue treatment.
    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 Decision2005-06-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-07-18
    P. End of Trial
    P.End of Trial StatusCompleted
    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA