Using Intensity Modulated Radiation Therapy (IMRT) for Brain Metastases

Phase I Dose Escalation Trial in Patients With Brain Metastases Using IMRT

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.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis
• Intervention / Treatment: Radiation: Intensity-Modulated Radiotherapy (IMRT)

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
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unacceptable Acute CNS Toxicity	The primary endpoint is the frequency of patients developing unacceptable acute CNS toxicity.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity (DLT)	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.	30 days

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: May 19, 2006
• First Submitted That Met QC Criteria: May 19, 2006
• First Posted (Estimate): May 22, 2006

Study Record Updates

• Last Update Posted (Estimate): October 21, 2016
• Last Update Submitted That Met QC Criteria: October 19, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: IMRT; Neoplasm; Brain metastases; Intensity Modulated Radiation Therapy; Parenchymal
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 05U.443; 2005-70 (Other Identifier: CCRRC); 05U.443R (Other Identifier: IRB)