Using Intensity Modulated Radiation Therapy (IMRT) for Brain Metastases

Phase 1

Completed

• Conditions: Neoplasm Metastasis
• Interventions: Radiation: Intensity-Modulated Radiotherapy (IMRT)

• Registration Number: NCT00328575
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2005-10
• Study First Submitted: 2006-05-19
• Study First Submitted QC: 2006-05-19
• Study First Posted: 2006-05-22
• Primary Completion: 2009-07
• Study Completion: 2011-06
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-19
• Last Update Posted: 2016-10-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intensity-Modulated Radiotherapy (IMRT)	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.

Primary Outcome Measures

Name	Time	Method
Unacceptable Acute CNS Toxicity	3 weeks	The primary endpoint is the frequency of patients developing unacceptable acute CNS toxicity.

Secondary Outcome Measures

Name	Time	Method
Dose-Limiting Toxicity (DLT)	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.

Trial Locations

Locations (1)

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States