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

Brain Metastases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00639262
• Other study ID #: 07P.381
• Secondary ID: 2006-58
• Status: Completed
• Phase: Phase 1
• First received: March 13, 2008
• Last updated: October 19, 2016
• Start date: March 2008
• Est. completion date: September 2012

Study information

• Verified date: October 2016
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Primary Brain Tumors

Intervention

Drug:
• Sorafenib
Sorafenib 200mg twice daily during XRT and 30 days after. (Sorafenib will be escalated for both cohorts to determine maximum tolerated dose)
• Temozolomide
For Cohort 2 - Gliomas only.

Radiation:
• Radiotherapy
Radiation Therapy (XRT)

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Cancer Center at Thomas Jefferson University	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Response Rate	Response rate (in those patients with measurable disease)	30 days post-treatment	No
Secondary	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	No
Secondary	Safety and Toxicity of Sorafenib	To evaluate the safety and toxicity profile of Sorafenib in combination with radiation therapy -/+ temozolomide	30 days post-treatment	Yes

External Links

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