The purpose of this trial is to show proof of concept that by blocking the Transforming Growth Factor-beta signaling pathway in patients with Glioblastoma, there will be clinical benefit.

Phase 1b: To determine the safe and tolerable dose of LY2157299 in combination with radiochemotherapy with temozolomide for Phase 2 in patients with glioma eligible to receive radiochemotherapy with temozolomide (e.g. newly diagnosed malignant glioma World Health Organization Grade III and IV).

Phase 2a: To confirm the tolerability and evaluate the pharmacodynamic effect of LY2157299 in combination with standard radiochemotherapy in patients with newly diagnosed glioblastoma.

Inclusion Criteria:

• Patients with histologically proven, newly diagnosed and untreated intracranial glioblastoma including lower grade glioma which evolved into glioblastoma and who have not received any radiochemotherapy or who have World Health Organization Grade III malignant glioma (e.g., Anaplastic Astrocytomas, Anaplastic Oligoastrocytomas, Anaplastic Oligodendroglioma) (Phase 1b only) will be eligible for this protocol
• Biopsy or resection must have been performed no more than 6 weeks prior to treatment
• An Magnetic Resonance Imaging must be obtained within 72 hours after surgery, preferably within 48 hours
• Patient must not have had prior cranial radiation therapy
• 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
• 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
• Patients must be willing to forego other cytotoxic and noncytotoxic drug therapy against the tumor while being treated with LY2157299 and temozolomide
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study
• Patients must have performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Patients must have adequate hematologic, hepatic and renal function
• Male and female patients with reproductive potential must use an approved contraceptive method,during and for 6 months after discontinuation of study treatment Women of childbearing potential must have a negative human chorionic gonadotropin pregnancy test documented within 14 days prior to treatment

Exclusion Criteria:

• 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

• 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
  • Have major abnormalities documented by echocardiography with Doppler
  • Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress

• Are unable to swallow tablets or capsules

• Are pregnant or breastfeeding

• 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

• 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

• Have active infection that would interfere with the study objectives or influence the study compliance

• Stereotactic radiosurgery, such as Gamma-Knife treatment, and brachytherapy are not allowed in this study