Randomized Trial Comparing Radiosurgery With vs Without Whole Brain Radiotherapy - Full Text View

Sponsored by:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00548756

Purpose

Primary Objectives:

To compare survival in a prospective randomized trial of patients with 1-3 brain metastases treated with either radiosurgery and whole brain radiation therapy or radiosurgery alone.
To prospectively compare the rates of local and distant brain recurrence between the two treatment groups.
To formally assess and compare neurocognitive changes and quality of life between the two treatment groups.
To determine after observation, when local salvage is an option, whether salvage therapy with local therapy (radiosurgery and/or surgery) can produce rates of freedom from progression comparable to WBRT by randomizing salvage therapy to be either local therapy or WBRT.
To use functional MRI to assess short-term memory by showing neuronal activation during picture recognition and to conduct dynamic susceptibility contrast-enhanced MRI to detect reductions in cerebral blood flow and blood volume that will allow monitoring of hemodynamic changes associated related to WBRT and metastatic brain disease.
To perform cost-utility analysis on randomized patients.

Condition	Intervention	Phase
Brain Cancer	Procedure: Whole Brain Radiation Therapy Other: Observation Behavioral: Questionnaire	Phase III

MedlinePlus related topics: Brain Cancer Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase III Prospective Randomized Trial Comparing Radiosurgery With Versus Without Whole Brain Radiotherapy for 1-3 Newly Diagnosed Brain Metastases

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

To learn if it is better to deliver whole brain radiation therapy immediately after radiosurgical treatment of 1-3 brain metastases or to carefully observe pts. after radiosurgery and hold back whole brain radiation therapy until the disease comes back. [ Time Frame: 8 Years ] [ Designated as safety issue: No ]

Estimated Enrollment:	152
Study Start Date:	January 2001
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Whole Brain Radiation Therapy	Procedure: Whole Brain Radiation Therapy Whole Brain Radiation Therapy. Total dose = 30 Gy over 12 fractions at 2.5Gy per fraction. Behavioral: Questionnaire Questionnaire taking 40 minutes to complete.
2 Observation	Other: Observation Patients who did not receive whole brain radiation and develop recurrent disease shall receive treatment based on the number of lesions. Behavioral: Questionnaire Questionnaire taking 40 minutes to complete.

Detailed Description:

TREATMENT:

Before treatment starts, patients will have a complete history (including details of previous chemotherapy, radiotherapy, and surgery for systemic disease). Patients will have a complete neuropsychological exam and will have their Karnofsky Performance Score (KPS) figured out. Seven cognitive function tests and a quality of life (QOL) questionnaire will be given to the patients as well. It will take about 40 minutes to complete the QOL questionnaire.

Patients in this study will be randomly picked (as in the toss of a coin) to be in one of two treatment groups. Patients in one group will receive immediate whole brain radiation therapy. Patients in the other group will hold off on radiation and just be closely observed. There is an equal chance of being in either group.

All patients will receive radiosurgery treatment to the known metastases (1-3 lesions) at the beginning. All participants will be followed with serial diagnostic and functional MRI. Experimental functional imaging will be used to evaluate short-term memory and picture recognition as well as blood flow within the brain.

Formal neuropsychological testing will also be performed at each follow-up interval. Patients will be seen for follow-up with neuropsychological evaluation, as well as diagnostic/function MRI at 1 , 2 , 4 , 6 , 9 , 12 , 15 , and 18 months and then every six months from then on. Each visit will require about 40 minutes of time.

Cost information related to protocol treatment and subsequent therapies will be tracked and collected for cost analysis between the two treatment groups.

Patients who did not receive whole brain radiation and develop recurrent disease shall receive treatment based on the number of lesions. If there are greater than 2 lesions, whole brain radiation will be given. If there are 1-2 lesions, patients will be randomly assigned to a local treatment (surgery or radiosurgery) or whole brain radiation therapy. Further recurrences in patients having not yet received whole brain radiation will be given this treatment at the time of recurrence.

The expected length of the study is 3.8 years with 6 months follow-up following the end of the study. Thus, the length of participation can range from 6 months for patients enrolling at the end of the study to over 4 years for patients enrolling at the beginning.

This is an investigational study. A total of 152 patients will take part in the study. All will be enrolled at M. D. Anderson.

Eligibility

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

Criteria

Inclusion Criteria:

Age 18 and older at time of registration.
Recursive partitioning class (RPA) I or II.
1 to 3 newly diagnosed brain metastases
Must be eligible to have all lesions treated by SRS as determined by the radiation oncologist on the basis of location and size.
MRI with contrast must be performed with 1 month of registration.
Signed informed consent form approved by the IRB agreeing to randomization.

Exclusion Criteria:

Prior WBRT
Prior resection of brain metastasis, SRS or Gamma knife.
> 3 brain metastases present on MRI
Lymphoma, small cell lung cancer, leukemia, germ cell tumors.
Leptomeningeal disease.
Unknown primary.
RPA Class III (i.e. KPS < 70)
Pregnancy.

Post-entry exclusion: No post-entry exclusions will be allowed after registration has occurred. All randomized patients will be included in the analysis and those lost to follow-up will be assigned the least favorable outcome (recurrence, death).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548756

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Eric L. Chang, MD

U.T.M.D. Anderson Cancer Center

More Information

MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Eric L. Chang, MD/Associate Professor )
Study ID Numbers:	ID00-377
Study First Received:	October 22, 2007
Last Updated:	December 8, 2008
ClinicalTrials.gov Identifier:	NCT00548756
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Brain Cancer
Whole Brain Radiation Therapy
Quality of Life
QOL

Questionnaire
Survey
WBRT

Study placed in the following topic categories:

Brain Neoplasms
Neoplasm Metastasis
Quality of Life
Central Nervous System Diseases

Central Nervous System Neoplasms
Brain Diseases
Nervous System Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on January 15, 2009