Brain Metastases, Primary Brain Tumors
Conditions
Keywords
Sorafenib, Radiation Therapy, Radiotherapy, Temozolomide, Brain Metastases, Brain Tumors
Brief summary
Sorafenib™ has the potential to inhibit tumor growth, tumor angiogenesis , and enhance radiation response. This study will test the combination of Sorafenib™ and radiation therapy with or without temozolomide to determine tolerance of the combined treatments. Defining safe dosing of Sorafenib™ in this combination therapy will be achieved.
Detailed description
The current standard of care for patients with brain metastatic malignancies is to receive radiation therapy alone, while the standard of care for patients with high grade primary brain malignancies, astrocytomas, is to receive to receive concurrent temozolomide with radiation therapy. In this phase I study, based on the range of efficacy of kinase inhibitors and its ability to cross the blood-brain barrier we will conduct two parallel studies. The first is to combine sorafenib and radiation therapy for the treatment of patients with brain metastases and the second is to combine sorafenib with temozolomide for primary brain tumors.
Interventions
DRUGSorafenib
Sorafenib 200mg twice daily during XRT and 30 days after. (Sorafenib will be escalated for both cohorts to determine maximum tolerated dose)
DRUGTemozolomide
For Cohort 2 - Gliomas only.
RADIATIONRadiotherapy
Radiation Therapy (XRT)
Sponsors
Bayer
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients requiring a minimum 2-week course of radiation therapy 2. Age \> or = 18 3. All tumors of the central nervous system, or metastasis to the central nervous system. 4. Measurable disease preferred but not required for eligibility 5. Histologically or cytologically documented evidence of malignancy (for infratentorial and supratentorial glioma patients only). 6. Radiographic evidence of brain metastasis 7. ECOG performance status of 0 or 1 8. Life expectancy of \> or = 3 months
Exclusion criteria
1. Patients receiving chemotherapy or other investigational drugs must be discontinued 14 days prior to enrollment. 2. Cardiac disease: Congestive heart failure \> class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months. 3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. 4. Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management. 5. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. 6. Active clinically serious infection \> CTCAE Grade 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose of Sorafenib | 30 days post-treatment | To determine the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D) of Sorafenib and radiotherapy -/+ temozolomide patients with malignancies of the brain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 30 days post-treatment | Response rate (in those patients with measurable disease) |
| Prediction of 1-year Recurrence | 1 year post-treatment | Determine if an increase in urinary VEGF and MMP levels, from the end of treatment to a patient's 1-month follow-up examination, is predictive of 1-year recurrence |
| Safety and Toxicity of Sorafenib | 30 days post-treatment | To evaluate the safety and toxicity profile of Sorafenib in combination with radiation therapy -/+ temozolomide |
Countries
United States
Outcome results
None listed