Using Intensity Modulated Radiation Therapy (IMRT) for Brain Metastases

Neoplasm Metastasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00328575
• Other study ID #: 05U.443
• Secondary ID: 2005-7005U.443R
• Status: Completed
• Phase: Phase 1
• First received: May 19, 2006
• Last updated: October 19, 2016
• Start date: October 2005
• Est. completion date: June 2011

Study information

• Verified date: October 2016
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2011
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

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.

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Cancer Center at Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Unacceptable Acute CNS Toxicity	The primary endpoint is the frequency of patients developing unacceptable acute CNS toxicity.	3 weeks	Yes
Secondary	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	Yes

External Links

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