Combination of Sorafenib and Radiation for Brain Metastases and Primary Brain Tumors

Sidney Kimmel Cancer Center at Thomas Jefferson University

Status and phase: Completed; Phase 1

Conditions: Brain Metastases; Primary Brain Tumors

Treatments: Radiation: Radiotherapy; Drug: Temozolomide; Drug: Sorafenib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00639262

JT 1208 (Other Identifier)

2006-58 (Other Identifier)

07P.381

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 2 patient groups

Cohort 1 - Brain Metastasis

Experimental group

Description:

Sorafenib and Radiotherapy

Treatment:

Drug: Sorafenib

Radiation: Radiotherapy

Cohort 2 - Gliomas

Experimental group

Description:

Sorafenib and Radiotherapy, plus Temozolomide

Treatment:

Drug: Sorafenib

Radiation: Radiotherapy

Drug: Temozolomide