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

Phase I Study of the Combination of Sorafenib and Radiation Therapy -/+ Temozolomide for the Treatment of Patients With Brain Metastases and Primary Brain Tumors

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.

Study Overview

• Status: Completed
• Conditions: Brain Metastases; Primary Brain Tumors
• Intervention / Treatment: Drug: Sorafenib; Radiation: Radiotherapy; Drug: Temozolomide

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 Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - Brain Metastasis; Sorafenib and Radiotherapy	Drug: Sorafenib; Sorafenib 200mg twice daily during XRT and 30 days after. (Sorafenib will be escalated for both cohorts to determine maximum tolerated dose); Other Names: Nexavar; Radiation: Radiotherapy; Radiation Therapy (XRT); Other Names: Radiation therapy; XRT; radiation oncology
Experimental: Cohort 2 - Gliomas; Sorafenib and Radiotherapy, plus Temozolomide	Drug: Sorafenib; Sorafenib 200mg twice daily during XRT and 30 days after. (Sorafenib will be escalated for both cohorts to determine maximum tolerated dose); Other Names: Nexavar; Radiation: Radiotherapy; Radiation Therapy (XRT); Other Names: Radiation therapy; XRT; radiation oncology; Drug: Temozolomide; For Cohort 2 - Gliomas only.; Other Names: Temodar; Temodal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose of Sorafenib	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.	30 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response rate (in those patients with measurable disease)	30 days post-treatment
Prediction of 1-year Recurrence	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	1 year post-treatment
Safety and Toxicity of Sorafenib	To evaluate the safety and toxicity profile of Sorafenib in combination with radiation therapy -/+ temozolomide	30 days post-treatment

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: Bayer
• Investigators: Principal Investigator: Adam Dicker, MD, PhD, Thomas Jefferson University

Publications and helpful links

Helpful Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: March 13, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimated): March 20, 2008

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: May 1, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Sorafenib; Temozolomide; Radiotherapy; Brain Tumors; Radiation Therapy; Brain Metastases
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide; Sorafenib
• Other Study ID Numbers: 07P.381; 2006-58 (Other Identifier: CCRRC); JT 1208 (Other Identifier: JeffTrial Number)