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

Phase 1

Completed

• Conditions: Primary Brain Tumors; Brain Metastases
• Interventions: Drug: Sorafenib; Drug: Temozolomide; Radiation: Radiotherapy

• Registration Number: NCT00639262
• Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

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.

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2008-03-13
• Study First Submitted QC: 2008-03-19
• Study First Posted: 2008-03-20
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-01
• Last Update Posted: 2025-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2 - Gliomas	Radiotherapy	Sorafenib and Radiotherapy, plus Temozolomide
Cohort 1 - Brain Metastasis	Radiotherapy	Sorafenib and Radiotherapy
Cohort 1 - Brain Metastasis	Sorafenib	Sorafenib and Radiotherapy
Cohort 2 - Gliomas	Sorafenib	Sorafenib and Radiotherapy, plus Temozolomide
Cohort 2 - Gliomas	Temozolomide	Sorafenib and Radiotherapy, plus Temozolomide

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States