primary glioma without methylation of the promoter gene of MGMT enzyme MedDRA version: 17.1 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Enzastaurin
Product Code: LY317615
Pharmaceutical Form: Tablet
INN or Proposed INN: Enzastaurin Hydrochloride
CAS Number: 170364-57-5
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: 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 ;Primary 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 (?), where ? is the exponential parameter. | — |
Countries
Germany
Outcome results
None listed