Clinical trial NCT00639262: Combination of Sorafenib and Radiation for Brain Metastases and Primary Brain Tumors
Official title: Phase I Study of the Combination of Sorafenib and Radiation Therapy -/+ Temozolomide for the Treatment of Patients With Brain Metastases and Primary Brain Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain Metastases
Primary Brain Tumors
Keywords: Sorafenib
Radiation Therapy
Radiotherapy
Temozolomide
Brain Metastases
Brain Tumors
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2008-03-20
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose of Sorafenib
timeFrame: 30 days post-treatment
Secondary outcomes:
measure: Response Rate
timeFrame: 30 days post-treatment
measure: Prediction of 1-year Recurrence
timeFrame: 1 year post-treatment
measure: Safety and Toxicity of Sorafenib
timeFrame: 30 days post-treatment
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Adam Dicker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: