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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00639262
First received: March 13, 2008
Last updated: March 27, 2014
Last verified: March 2014
  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 1

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:


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 2015
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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00639262     History of Changes
Other Study ID Numbers: 07P.381, 2006-58
Study First Received: March 13, 2008
Last Updated: March 27, 2014
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
Neoplasms, Second Primary
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms by Site
Neoplastic Processes
Nervous System Diseases
Nervous System Neoplasms
Pathologic Processes
Sorafenib
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014