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    Summary
    EudraCT Number:2007-000281-21
    Sponsor's Protocol Code Number:H6Q-MC-S039
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-08-15
    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 ConcernedGermany - BfArM
    A.2EudraCT number2007-000281-21
    A.3Full title of the trial
    Enzastaurin (LY317615) Before and Concomitant with Radiation Therapy, Followed by Enzastaurin Maintenance Therapy in Patients with Newly Diagnosed Glioblastoma without Methylation of the Promoter Gene of MGMT Enzyme
    – a Multicenter, Open-label, Uncontrolled Phase II Study
    A.4.1Sponsor's protocol code numberH6Q-MC-S039
    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 SponsorEli Lilly and Company
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsor
    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 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 nameEnzastaurin
    D.3.2Product code LY317615
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNEnzastaurin Hydrochloride
    D.3.9.1CAS number 170364-57-5
    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) 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 No
    D.3.11.8Extractive medicinal product No
    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
    primary glioma without methylation of the promoter gene of MGMT enzyme
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10018336
    E.1.2Term Glioblastoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Information not present in EudraCT
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The study’s primary objective is evaluation of PFS-6 after diagnosis in patients with newly diagnosed glioblastoma without methylation of the promoter gene of MGMT enzyme treated with enzastaurin before and concomitantly to radiation therapy, followed by enzastaurin maintenance therapy.
    In a safety run- in phase, 2 dose regimen of enzastaurin will be explored: 500 mg given in one daily dose (QD) and two daily doses of 250 mg (BID) to proof the safety of the QD and BID regimen plus radiotherapy.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are as follows:
    • investigate safety and tolerability as measured by NCI-CTC Version 3.0 criteria
    • investigate changes in neurologic status as measured by clinical neurologic examination and Mini Mental Status (MMST) questionnaire
    • assess response rates according to the criteria defined by MacDonald et al. 1990
    • evaluate survival including 1 and 2 year survival rates
    • assess biomarkers relevant to enzastaurin and disease state, and their correlation to clinical outcome
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients are eligible to be included in the study only if they meet all of the following criteria:
    [1] Present with newly diagnosed histologically proven supratentorial Glioblastoma multiforme (GBM) (WHO [World Health Organization] grade IV). The histological diagnosis can be obtained either from a brain biopsy or from a neurosurgical resection of the tumor.
    [2] demonstration of an unmethylated MGMT-promotor, that is activity of the MGMT-gene, in a methylation-sensitive PCR
    [3] Patients must sign an informed consent document.
    [4] Patients must be at least 18 years of age.
    [5] estimated life expectancy of at least 12 weeks
    [6] patient compliance and geographic proximity that allow for adequate follow-up
    [7] Tumor tissue specimens (paraffin-embedded and/or frozen) from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of PKCß targets (for example, GSK3ß).
    [8] disease evaluated by Gd-MRI (magnetic resonance imaging) within 72 hours postoperatively
    [9] interval of ≥2 and ≤4 weeks since surgery or biopsy before first administration of enzastaurin
    [10] ECOG Performance Status of ≤2
    [11] Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test ≤14 days prior to study enrollment.
    [12] adequate organ function including the following:
    • adequate bone marrow reserve
    • hepatic: bilirubine ≤1.5 times the upper limit of normal (x ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT)
    ≤2.5 X ULN, or <5 x ULN with liver metastases
    • renal: serum creatinine <1.5 x ULN
    • blood clotting: prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits
    [13] Patients must discontinue use of enzyme-inducing antiepileptic drugs (EIAEDs) ≥14 days prior to study enrollment. The investigator may prescribe non-EIAEDs . Patients who must begin EIAED therapy while on study will be allowed to remain on study.
    [14] Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG); no history of stroke
    E.4Principal exclusion criteria
    Patients will be excluded from the study if they meet any of the following criteria:
    [15] have a prior malignancy (other than glioblastoma, or adequately treated carcinoma in situ of the cervix, or nonmelanoma skin cancer), unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
    [16] unable to undergo Gd MRI
    [17] prior chemotherapy within the last 5 years
    [18] prior chemotherapy for a brain tumor
    [19] prior radiotherapy of the head
    [20] are receiving concurrent administration of any other antitumor therapy
    [21] are unable to swallow tablets
    [22] are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin
    [23] planned surgery for other diseases (for example, dental extraction)
    [24] history of coagulation disorder associated with bleeding, or recurrent thrombotic events
    [25] are receiving concurrent administration of anticoagulant therapy.
    However, if a patient requires anticoagulant therapy after starting treatment, the patient may remain on study therapy. If possible, warfarin should not be used as anticoagulant therapy. Anticoagulant therapy may include low-molecular weight heparin.
    [26] placement of Gliadel® wafer at surgery
    [27] have a serious concomitant systemic disorder (for example, active infection including HIV, or cardiac disease) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. Patients with a QTc prolongation >450/470 msec (males/females) and patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded, at the investigator’s discretion. The investigator should consider the life-threatening nature of GBD and the overall potential risk and benefit to the patient.
    [28] known hypersensitivity to the study treatment
    [29] current alcohol dependence or drug abuse
    [30] legal incapacity or limited legal capacity
    [31] patients who are pregnant, anticipate becoming pregnant within 6 months after study participation, or are currently breast-feeding
    [32] have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint for this trial is progression-free survival at 6 months. The primary analysis will be the estimation of the PFS-6 rate using Kaplan-Meier techniques (Kaplan and Meier 1958). According to the sample size calculation a 95% CI will be presented using the asymptotic normality of log (λ), where λ is the exponential parameter.
    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 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.8.3 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 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 Information not present in EudraCT
    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
    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 months5
    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 months5
    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.1.3Elderly (>=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 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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 60
    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)
    Subsequent treatment of patients that discontinue study treatment is up to the discretion of the treating physician. There is no specific post-study therapy mandated by the protocol.
    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 Decision2007-06-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-09-05
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-03-24
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