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

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)

Overall Status

Completed

CT.gov ID

NCT00639262

Collaborator

Bayer (Industry)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases Primary Brain Tumors	Drug: Sorafenib Drug: Temozolomide Radiation: Radiotherapy	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

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: XRT Radiation therapy 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 Drug: Temozolomide For Cohort 2 - Gliomas only. Other Names: Temodar Temodal Radiation: Radiotherapy Radiation Therapy (XRT) Other Names: XRT Radiation therapy radiation oncology

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:

XRT

Radiation therapy

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

Drug: Temozolomide

For Cohort 2 - Gliomas only.

Other Names:

Temodar

Temodal

Radiation: Radiotherapy

Radiation Therapy (XRT)

Other Names:

XRT

Radiation therapy

radiation oncology

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients requiring a minimum 2-week course of radiation therapy
Age > or = 18
All tumors of the central nervous system, or metastasis to the central nervous system.
Measurable disease preferred but not required for eligibility
Histologically or cytologically documented evidence of malignancy (for infratentorial and supratentorial glioma patients only).
Radiographic evidence of brain metastasis
ECOG performance status of 0 or 1
Life expectancy of > or = 3 months

Exclusion Criteria:

Patients receiving chemotherapy or other investigational drugs must be discontinued 14 days prior to enrollment.
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.
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
Active clinically serious infection > CTCAE Grade 2