Using Intensity Modulated Radiation Therapy (IMRT) for Brain Metastases

This study has been completed.
Sponsor:
Information provided by:
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00328575
First received: May 19, 2006
Last updated: August 2, 2011
Last verified: August 2011
  Purpose

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 Intervention Phase
Neoplasm Metastasis
Radiation: Intensity-Modulated Radiotherapy (IMRT)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Trial in Patients With Brain Metastases Using IMRT

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Unacceptable Acute CNS Toxicity [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    The primary endpoint is the frequency of patients developing unacceptable acute CNS toxicity.


Secondary Outcome Measures:
  • Dose-Limiting Toxicity (DLT) [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 10
Study Start Date: October 2005
Study Completion Date: June 2011
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  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: NCT00328575

Locations
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Wenyin Shi, MD, PhD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Wenyin Shi, MD, PhD, Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00328575     History of Changes
Other Study ID Numbers: 05U.443, 2005-70, 05U.443R
Study First Received: May 19, 2006
Last Updated: August 2, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
Brain metastases
Parenchymal
Neoplasm
IMRT
Intensity Modulated Radiation Therapy

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

ClinicalTrials.gov processed this record on October 20, 2014