A Study Combining LY2157299 With Temozolomide-based Radiochemotherapy in Patients With Newly Diagnosed Brain Cancer
- Conditions
- Glioblastoma Multiforme (GBM)MedDRA version: 14.1Level: PTClassification code 10018337Term: Glioblastoma multiformeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-022160-13-DE
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 62
Patients are eligible only if they meet all of the following criteria:
[1]Patients with histologically proven, newly diagnosed and untreated intracranial GBM including lower grade glioma which evolved into GBM and who have not received any radiochemotherapy (Phase 1b and 2a) or who have WHO Grade III and IV malignant glioma (e.g., AA, AO, AOA) (Phase 1b only) and for Phase 2a, only WHO Grade IV will be eligible for this protocol (Louis et al. 2007).
[2]A biopsy or resection must have been performed no more than 6 weeks prior to treatment. During Phase 1b, the interval may be greater than 6 weeks.
•One or two stained slides from the stereotactic biopsy or open surgery must be available for central pathology review to confirm the original diagnosis.
•If available an FFPE tissue block or unstained slides are to be submitted for pharmacodynamic assessment. If a sample is not available, such a patient will be kept in study and this will not constitute a protocol violation. Additional patients may be enrolled to the trial to ensure an appropriate number of samples are available for the evaluation of the pharmacodynamic markers.
[3]An MRI must be obtained within 72 hours after surgery, preferably within 48 hours. In exceptional situations, the MRI can also be performed up to 96 hours after surgery. In such cases the investigators must deem the MRI image acceptable for subsequent assessments. Patients without measurable or assessable disease are eligible.
For Part 1b, failure of taking the MRI image in the prescribed interval will not constitute a protocol violation, because the objective is on safety.
For Part 2a, failure of taking the MRI image in the prescribed interval will require the addition of a patient to this study to ensure sufficient numbers to assess responses.
[4]Patient must not have had prior cranial RTX.
[5]Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors. Patients who received Gliadel® wafers at the time of original resection will be excluded.
[6]Patients must plan to begin partial brain radiotherapy within 2-6 weeks after surgery. Regular fractionated radiotherapy with photons (in any planning mode and possibly image-guided or stereotactic if deemed necessary) is performed according to the discretion of the investigator. During Phase 1b, the interval may be greater than 6 weeks.
[7]Patients must be willing to forego other cytotoxic and noncytotoxic drug therapy against the tumor while being treated with LY2157299 and TMZ.
[8]All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
[9]Patients must be >18 years old
[10]Patients must have performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale (see Protocol Attachment JBAI.5.)
[11]Patients must have adequate organ function, demonstrated by the following tests, which must be performed within 14 days prior to treatment:
•Adequate bone marrow reserve: white blood cell (WBC) count ?3.0 ? 109/L, absolute neutrophil count (ANC) ?1.5 ? 109/L, platelet count ?100.0 ? 109/L, and hemoglobin ?10.0 g/dL (6.2 mmol/L). Eligibility level for hemoglobin may be reached by transfusion, if the hemoglobin is ?9.0 g/dL.
•Hepatic: bilirubin ?2.0 times the upper limit of normal (ULN); alkaline phosphatase (ALP), aspartate transaminase (AST/SGOT), and alanine transaminase (ALT/
Patients will be excluded if they meet any of the following criteria:
[13]Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or not approved use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
[14]Have moderate or severe cardiac disease as defined by any of the following:
•Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension.
•Have documented major electrocardiogram (ECG) abnormalities that are symptomatic and are not medically controlled (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle branch blocks, ventricular hypertrophy, or recent myocardial infarction).
•Have major abnormalities documented by echocardiography with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction (LVEF) <50%, evaluation based on the institutional lower limit of normal). For additional details, refer to echocardiography protocol (Protocol Attachment JBAI.7).
•Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by CT scan with contrast).
[15]Are unable to swallow tablets or capsules.
[16]Are pregnant or breastfeeding.
[17]Have any significant medical illnesses that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy.
[18]Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and stopped all therapy for that disease for a minimum of 3 years are ineligible.
[19]Have active infection that would interfere with the study objectives or influence the study compliance.
[20]Stereotactic radiosurgery, such as Gamma-Knife treatment, and brachytherapy are not allowed in this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method