Combination of Sorafenib and Radiation for Brain Metastases and Primary Brain Tumors - Full Text View

Sponsor:	Thomas Jefferson University
Collaborator:	Bayer
Information provided by (Responsible Party):	Thomas Jefferson University
ClinicalTrials.gov Identifier:	NCT00639262

Purpose

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	Intervention	Phase
Brain Metastases Primary Brain Tumors	Drug: Sorafenib Drug: Temozolomide Radiation: Radiotherapy	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Temozolomide Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:

Maximum Tolerated Dose of Sorafenib [ Time Frame: 30 days post-treatment ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 30 days post-treatment ] [ Designated as safety issue: No ]
Response rate (in those patients with measurable disease)
Prediction of 1-year Recurrence [ Time Frame: 1 year post-treatment ] [ Designated as safety issue: No ]
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 [ Time Frame: 30 days post-treatment ] [ Designated as safety issue: Yes ]
To evaluate the safety and toxicity profile of Sorafenib in combination with radiation therapy -/+ temozolomide

Enrollment:	35
Study Start Date:	March 2008
Estimated Study Completion Date:	March 2013
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00639262

Locations

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

Sponsors and Collaborators

Thomas Jefferson University

Bayer

Investigators

Principal Investigator:

Adam Dicker, MD, PhD

Thomas Jefferson University

More Information

Additional Information:

Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center This link exits the ClinicalTrials.gov site

Thomas Jefferson University Hospitals This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Thomas Jefferson University
ClinicalTrials.gov Identifier:	NCT00639262 History of Changes
Other Study ID Numbers:	07C.381, 2006-58
Study First Received:	March 13, 2008
Last Updated:	January 10, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:

Sorafenib
Radiation Therapy
Radiotherapy

Temozolomide
Brain Metastases
Brain Tumors

Additional relevant MeSH terms:

Brain Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplastic Processes
Pathologic Processes

Temozolomide
Dacarbazine
Sorafenib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012