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A Prospective Phase III Trial to Compare Stereotactic Radiosurgery Versus Whole Brain Radiation Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01592968
First received: May 3, 2012
Last updated: August 21, 2014
Last verified: August 2014

May 3, 2012
August 21, 2014
August 2012
August 2016   (final data collection date for primary outcome measure)
  • Local Tumor Control [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Lesions assessed using contrast-enhanced MRI scans. Progressive disease (PD) considered local failure, or stable disease with deterioration of neurological examination with a grade III or worse toxicity on the CTC AE v.4.0 scale. Local control measured by contrast-enhanced brain MRI scan using modified RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in sum of diameters of target lesions. Progressive Disease (PD): At least a 20% increase in sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For local control, PD considered local failure, or stable disease with deterioration of neurological examination with a grade III or worse toxicity on the CTC AE v.4.0 scale. All others (CR, PR, asymptomatic SD) are deemed success.
  • Cognitive Decline [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Baseline Hopkins Verbal Learning Testing-Revised (HVLT-R) score compared to HVLT-R score in patients surviving 4 months. Preservation of function defined as improvement of HVLT-R score or decline by 4 points or less. Failure defined as decline by 5 or more points. Time to neurocognitive decline estimated for each treatment arm using product limit estimator of Kaplan and Meier.
  • Local Tumor Control [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Local control rates estimated at 4 months for each treatment arm with 95% confidence intervals based on the Kaplan-Meier estimates of time to local failure. Logrank test stratified by stratification factors used at randomization to compare the 2 treatment arms with respect to time to local failure. Lesions assessed using contrast-enhanced MRI scans. Progressive disease (PD) is considered local failure, or stable disease with deterioration of the neurological examination with a grade III or worse toxicity on the CTC AE v.4.0 scale.
  • Cognitive Decline [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Baseline HVLT-R score compared to HVLT-R score in patients surviving 4 months. Preservation of function defined as improvement of HVLT-R score or decline by 4 points or less. Failure defined as decline by 5 or more points. Time to neurocognitive decline estimated for each treatment arm using product limit estimator of Kaplan and Meier.
Complete list of historical versions of study NCT01592968 on ClinicalTrials.gov Archive Site
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A Prospective Phase III Trial to Compare Stereotactic Radiosurgery Versus Whole Brain Radiation Therapy
A Prospective Phase III Randomized Trial to Compare Stereotactic Radiosurgery Versus Whole Brain Radiation Therapy for >/= 4 Newly Diagnosed Non-Melanoma Brain Metastases

The goal of this clinical research study is to compare stereotactic radiosurgery to whole brain radiation therapy in patients with 4-10 non-melanoma brain tumors.

Stereotactic radiosurgery is the delivery of focused, high-dose radiation given in a single session to the tumors with a minimal dose given to uninvolved areas of the brain.

Whole brain radiation is the delivery of lower dose radiation to the entire brain given daily over 2 weeks.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being assigned to either group:

  • If you are in Group 1, you will receive whole brain radiation treatment.
  • If you are in Group 2, you will receive stereotactic radiosurgery.

Study Procedures:

If you are in Group 1, you will receive whole brain radiation treatment each day, Monday-Friday starting on Day 1. If you are an inpatient, you may receive radiation treatment on weekends as well. You will continue to receive radiation treatment up to Day 14.

If you are in Group 2, you will receive stereotactic radiosurgery on Day 1. As part of the stereotactic radiosurgery procedure, you will receive a very accurate kind of MRI scan on the morning of the procedure. If this MRI scan identifies more tumors, you may still continue to participate in the study with up to 15 tumors. If there are more than 15 tumors found on the treatment planning MRI scan on the day of the SRS treatment, then you are not eligible to participate in the study. In this case, your study doctor will discuss with you other treatment options off of the study, which may include stereotactic radiosurgery and/or whole brain radiation therapy.

No matter which group you are in, you will sign a separate consent form for whole brain radiation or stereotactic radiosurgery that will explain the procedures and risks in detail.

Study Visits:

At 1, 4, 6, 9, and 12 months (+/- 14 days) after your assigned treatment, you will return to the clinic:

  • You will have a physical exam, including measurement of your vital signs.
  • You will be asked about any drugs you may be taking.
  • You will have an MRI scan to check the status of the disease.
  • You will complete the 7 cognitive function tests.
  • You will complete 3 questionnaires that ask about your quality of life and any symptoms you may be having.

Length of Study Participation:

Your active participation on the study will be over when you have completed the follow-up visits.

Follow-Up Visits:

If the study doctor thinks it is needed, you will return to the clinic for follow-up visits. The following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs.
  • You will be asked about any drugs you may be taking.
  • You will have an MRI to check the status of the disease.

This is an investigational study. It is considered investigational to compare stereotactic radiosurgery to whole brain radiation therapy in patients with 4-10 non-melanoma brain tumors.

Up to 100 patients will take part in this study. All will be enrolled at MD Anderson.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain Neoplasms
  • Radiation: Stereotactic Radiosurgery (SRS)
    Dose based on largest diameter lesion as measured on volumetric MRI, as follows: 20-24 Gy for lesions 2 cm or less in size, 16-18 Gy for lesions >2-2.5 cm in size, and 12-16 Gy for lesions >2.5-3.5 cm in size. SRS performed on day 1.
    Other Names:
    • XRT
    • Radiation therapy
  • Radiation: Whole Brain Radiation Therapy (WBRT)
    Fractionated radiation delivered to whole brain daily to deliver a dose of 30 Gy in 10 fractions.
    Other Names:
    • XRT
    • Radiation therapy
  • Behavioral: Questionnaires
    Three (3) sets of quality of life (QOL) questionnaires completed 1, 4, 6, 9, and 12 months after assigned treatment.
    Other Name: Surveys
  • Behavioral: Cognitive Function Tests
    7 cognitive function tests completed 1, 4, 6, 9, and 12 months after assigned treatment.
  • Experimental: Stereotactic Radiosurgery (SRS)
    Dose based on largest diameter lesion as measured on volumetric MRI, modified as follows: 20-24 Gy for lesions 2 cm or less in size, 16-18 Gy for lesions >2-2.5 cm in size, and 12-16 Gy for lesions >2.5-3.5 cm in size. SRS performed on day 1.
    Interventions:
    • Radiation: Stereotactic Radiosurgery (SRS)
    • Behavioral: Questionnaires
    • Behavioral: Cognitive Function Tests
  • Experimental: Whole Brain Radiation Therapy (WBRT)
    Fractionated radiation delivered to whole brain daily to deliver a dose of 30 Gy in 10 fractions.
    Interventions:
    • Radiation: Whole Brain Radiation Therapy (WBRT)
    • Behavioral: Questionnaires
    • Behavioral: Cognitive Function Tests
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
Not Provided
August 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. All patients must have histological proof of malignant cancer, which is metastatic. Histological proof may be obtained from the primary tumor or another metastatic site. However, cytology alone is not an acceptable method of diagnosis.
  2. All patients must have greater than 3 but less than or equal to 10 metastatic lesions seen on a contrast enhancing MRI scan obtained not less than one month prior to study enrollment. Patients who are found to have 11-15 metastatic lesions at the time of treatment planning (on volumetric MRI once the head frame is in place) may still participate in the trial.
  3. All patients must be >/= 18 years of age.
  4. All patients must sign informed consent verifying that they are aware of the investigational nature of this study in keeping with the rules and policies of M.D. Anderson Cancer Center. The only acceptable consent form is the one attached at the end of this protocol, and it must have been approved and amended by the M.D. Anderson IRB.
  5. All patients must be eligible to have all lesions treated with SRS (i.e. maximum diameter of largest lesion < 3.5cm) as determined by the radiation oncologist .
  6. All patients must have adequate liver, renal, and hematologic function as defined by Aspartate Amino Transferase (AST)/Alanine Amino Transferase (ALT)/Alkaline Phosphatase < 2.5 times normal, calculated creatinine clearance > 30ml/min, and platelet count > 50,000.
  7. All patients should have normal coagulation, with international normalized ratio (INR) < 1.3 and able to withhold anti-coagulation medications a minimum of 24 hours prior to radiosurgery (or until INR normalizes), on the day of treatment and 24 hours after radiosurgery has concluded. Those patients getting WBRT may continue these medications.
  8. Patients can be undergoing concurrent systemic therapy, such as temozolomide, at the discretion of their treating oncologist.

Exclusion Criteria:

  1. Patients are excluded from this trial if they have melanoma, small cell carcinoma, lymphoma/leukemia, or germ cell histology (note, melanoma patients will be eligible for the sister trial to this trial which will be open simultaneously).
  2. Patients will be excluded if they have had prior surgical resection of metastatic cancer from the brain.
  3. Patients will be excluded if there is radiographic or CSF cytological evidence of leptomeningeal disease.
  4. Patients will be excluded if they have had prior radiation to the brain (either WBRT, prophylactic cranial irradiation (PCI), or SRS).
  5. Female patients of childbearing age will be excluded if they are pregnant as assessed by serum b-HCG or urine pregnancy test. A serum b-HCG test or urine pregnancy test will be performed no greater than 14 days prior to study registration.
  6. Patients will be excluded if they are unable to obtain an MRI scan.
  7. Patients will be excluded if they have < 4 lesions, or > 10 lesions at enrollment or > 15 lesions at the time of treatment (note: patients who qualify for enrollment based on having 4-10 lesions, but who are discovered to have 11-15 lesions on the volumetric MRI used for treatment planning will be allowed to continue on study).
Both
18 Years and older
No
Contact: Jing Li, MD 713-563-2300
United States
 
NCT01592968
2011-0884, NCI-2012-00850
Yes
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Not Provided
Principal Investigator: Jing Li, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP