Using Intensity Modulated Radiation Therapy (IMRT) for Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00328575
Recruitment Status : Completed
First Posted : May 22, 2006
Last Update Posted : October 21, 2016
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Brief Summary:
The purpose of this study is to determine if using intensity modulated radiation therapy for brain metastases is safe and will improve local control more than standard whole brain radiation therapy.

Condition or disease Intervention/treatment Phase
Neoplasm Metastasis Radiation: Intensity-Modulated Radiotherapy (IMRT) Phase 1

Detailed Description:

Traditionally, whole brain radiation therapy (WBRT) has been the primary therapy for patients with brain metastases. Despite this therapy, patients still have poor survival of four to six months. Untreated patients have a median survival of one month. Up to one half of these patients die of causes related to the presence of brain metastases. In a Phase I/II RTOG trial, the efficacy and safety of delivering accelerated fractionation was investigated in patients with good prognostic factors. No toxicity was observed with escalating dose of irradiation up 70.40Gy in 1.6Gy twice daily treatments. However, in a randomized trial, the use of hyperfractionation did not appear to improve survival when compared to 30Gy whole brain irradiation delivered in 10 fractions.

Current therapeutic approach also includes stereotactic radiosurgery (SRS). Several retrospective studies have demonstrated improved local tumor control of 80% with addition of SRS to WBRT. These local control rates were comparable to surgery. In a recently published randomized trial by RTOG 95-08 (TJU accrued 42 patients to this trial), Andrews et al. demonstrated improved survival in patients with solitary brain lesion treated with SRS. Median survival was 6.5 months in patients treated with WBRT and SRS compared to 4.9 months in patients treated with WBRT alone. Also, these patients were more likely to have stable or improved performance status.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Trial in Patients With Brain Metastases Using IMRT
Study Start Date : October 2005
Actual Primary Completion Date : July 2009
Actual Study Completion Date : June 2011

Arm Intervention/treatment
Experimental: Intensity-Modulated Radiotherapy (IMRT)
Patients with brain metastases will be enrolled in one of three dose levels based on tumor size. For tumor size of 3 cm or less (maximum diameter in any dimension), doses of 47.5Gy, 52.5Gy, and 54.5Gy will be tested. For tumor size of greater than 3 cm (maximum diameter in any dimension), doses of 42.5Gy, 47.5Gy, and 52.5Gy will be tested.
Radiation: Intensity-Modulated Radiotherapy (IMRT)

The duration of radiation therapy will be total of 3 weeks. During the first week, all patients will be treated initially with whole brain radiation therapy (WBRT) at 2.5Gy per fraction daily 5 days a week to a dose of 12.5Gy. This will be delivered through parallel-opposed fields to cover the entire cranial contents.

For the remaining 2 weeks, patients will be treated using intensity-modulated radiation therapy (IMRT) technology such that a higher dose can be delivered to the tumor. IMRT is capable of generating complex 3-D dose distribution to conform closely to the target volume by modulating the radiation beam. This process is based on the "inverse method" of treatment planning to optimize radiation dose to tumor target coverage and normal tissue sparing.

Other Name: Radiation Therapy

Primary Outcome Measures :
  1. Unacceptable Acute CNS Toxicity [ Time Frame: 3 weeks ]
    The primary endpoint is the frequency of patients developing unacceptable acute CNS toxicity.

Secondary Outcome Measures :
  1. Dose-Limiting Toxicity (DLT) [ Time Frame: 30 days ]
    Dose-limiting toxicity will be defined as Grade 3 or greater CNS toxicity, as per NCI criteria. The observed rate of > 30% of Grade 3 or greater acute CNS toxicities will be considered unacceptable. Late toxicities will be closely monitored as well.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed malignancy
  • 2-5 parenchymal brain metastases on magnetic resonance imaging (MRI) with a maximum size of 4 cm
  • Partial resection allowed. Complete resection allowed only in patients with more than 3 lesions.
  • Karnofsky Performance Status (KPS) equal to or greater than 60
  • Neurologic function equal to or greater than 2

Exclusion Criteria:

  • Recurrent brain tumors
  • Major medical or psychiatric illnesses
  • Metastases in brainstem, midbrain, pons, or medulla
  • Patients with leukemia or lymphoma

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00328575

United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Sidney Kimmel Cancer Center at Thomas Jefferson University
Principal Investigator: Wenyin Shi, MD, PhD Thomas Jefferson University

Additional Information:
Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University Identifier: NCT00328575     History of Changes
Other Study ID Numbers: 05U.443
2005-70 ( Other Identifier: CCRRC )
05U.443R ( Other Identifier: IRB )
First Posted: May 22, 2006    Key Record Dates
Last Update Posted: October 21, 2016
Last Verified: October 2016

Keywords provided by Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University ):
Brain metastases
Intensity Modulated Radiation Therapy

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes