Metastatic Malignant NeoplasmPhase 3NCT01592968
Stereotactic Radiosurgery or Whole Brain Radiation Therapy in Treating Patients With Newly Diagnosed Non-melanoma Brain Metastases
A Phase 3 study testing Cognitive Assessment, Quality-of-Life Assessment and Stereotactic Radiosurgery in people with Metastatic Malignant Neoplasm and Metastatic Malignant Neoplasm in the Brain, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This randomized phase III clinical trial compares stereotactic radiosurgery with whole brain radiation therapy to see how well they work in treating patients with non-melanoma cancer that has recently spread from the first location to the brain. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Neoplasm, Metastatic Malignant Neoplasm in the Brain
- What is being tested?
- Cognitive Assessment, Quality-of-Life Assessment and Stereotactic Radiosurgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Aug 2012to 30 Sep 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- All patients must have greater than 3 but less than or equal to 15 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 up to 20 metastatic lesions at the time of treatment planning (on volumetric MRI once the head frame is in place) may still participate in the trial.
- All patients must be >/= 18 years of age.
- 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.
- 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 .
- 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.
- 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.
- Patients can be undergoing concurrent systemic therapy, such as temozolomide, at the discretion of their treating oncologist.
Who cannot join
- 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).
- Patients will be excluded if they have had prior surgical resection of metastatic cancer from the brain.
- Patients will be excluded if there is radiographic or CSF cytological evidence of leptomenengial disease.
- Patients will be excluded if they have had prior Whole Brain Radiotherapy (WBRT) or prophylactic cranial irradiation (PCI). Prior SRS or Gamma Knife radiosurgery to 1-3 metastases with minimum of (6) weeks to the most recent scan are allowed on protocol.
- 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.
- Patients will be excluded if they are unable to obtain an MRI scan.
- Patients will be excluded if they have < 4 lesions, or > 15 lesions at enrollment or > 20 lesions at the time of treatment (note: patients who qualify for enrollment based on having 4-15 lesions, but who are discovered to have up to 20 lesions on the volumetric MRI used for treatment planning will be allowed to continue on study).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Phase III Randomized Trial to Compare Stereotactic Radiosurgery vs. Whole Brain Radiation Therapy for >/= 4 Newly Diagnosed Non-Melanoma Brain Metastases
This randomized phase III clinical trial compares stereotactic radiosurgery with whole brain radiation therapy to see how well they work in treating patients with non-melanoma cancer that has recently spread from the first location to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic radiosurgery is a specialized type of radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Whole brain radiation therapy delivers a lower dose of radiation to the entire brain over several treatments. It is not yet known whether stereotactic radiosurgery works better than whole brain radiation therapy in treating patients with non-melanoma brain metastases. Stereotactic radiosurgery may also cause fewer thinking and memory problems than whole brain radiation therapy.
Read the detailed description
PRIMARY OBJECTIVES:
- To compare local tumor control 4 months after treatment of patients with 4 to 15 intracranial non-melanoma metastases at the time of enrollment (=< 15 at time of treatment) treated with stereotactic radiosurgery (SRS) versus (vs.) whole brain radiation therapy (WBRT) in a prospective randomized trial.
II. To compare cognitive decline at 4 months defined as a significant decline (5 point decrease from baseline based on the reliable change index) in Hopkins Verbal Learning Test - Revised (HVLT-R) Total Recall after initial treatment with stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with 4 to 15 non-melanoma brain metastases at the time of enrollment (=< 15 at time of treatment).
SECONDARY OBJECTIVES:
- To determine local control and distant tumor control in the brain at 1, 4, 6, 9, and 12 months post treatment.
II. To determine overall survival in each treatment arm. III. To assess the pattern of neurocognitive change in memory at 1, 4, 6, 9, and 12 months post-treatment as well as executive function, attention, processing speed, and upper extremity fine motor dexterity.
IV. To evaluate the composite neurocognitive function score for both treatment arms.
- To assess the pre-treatment factors of age, Karnofsky performance status (KPS), and extra-cranial disease in the predictive determination of local and distant control and neurocognitive outcome in each treatment arm.
VI. To assess the correlation between number of lesions and total volume of intracranial disease and neurocognitive outcome in each treatment arm.
VII. To compare time to initiation of systemic therapy from completion of radiotherapy between the two treatment arms.
VIII. To compare number of cycles of systemic therapy delivered following completion of radiation treatment in the two treatment arms.
IX. To document and descriptively compare post-treatment adverse side effects between the two treatment arms.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo SRS on day 1.
ARM II: Patients undergo WBRT 5 days per week (7 days per week for inpatients) for 2 weeks.
After completion of study treatment, patients are followed up at 1, 4, 6, 9, and 12 months.
- Being tested
- Cognitive Assessment, Quality-of-Life Assessment, Stereotactic Radiosurgery, Whole-Brain Radiotherapy
- Medical subject headings
- Neoplasm Metastasis, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive AssessmentOther
Ancillary studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Stereotactic RadiosurgeryRadiation
Also called Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, stereotactic radiation therapy, Stereotactic Radiotherapy
Undergo SRS
Whole-Brain RadiotherapyRadiation
Also called WBRT, whole-brain radiation therapy
Undergo WBRT
| Study group | Role | What they receive |
|---|---|---|
| Arm I (SRS) | Experimental | Patients undergo SRS on day 1. Receives: Other: Cognitive Assessment; Other: Quality-of-Life Assessment; Radiation: Stereotactic Radiosurgery |
| Arm II (WBRT) | Experimental | Patients undergo WBRT 5 days per week (7 days per week for inpatients) for 2 weeks. Receives: Other: Cognitive Assessment; Other: Quality-of-Life Assessment; Radiation: Whole-Brain Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local control rate
Estimated for each treatment arm with 95% confidence intervals based on the estimates of time to local failure.
Measured: At 4 months
Proportion of patients with neurocognitive decline
Defined as a decline of 5 or more points from baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) score. Estimated for each treatment arm with 95% confidence intervals based on the estimates of time to neurocognitive decline.
Measured: At 4 months
Secondary outcomes (4)
Time to local failure
Estimated using the product-limit estimator for each treatment arm. The logrank test stratified by the stratification factors will be used at randomization to compare the 2 treatment arms with respect to the time to local failure.
Measured: Up to 12 months
Cumulative incidence of local failure
Estimated with death as a competing event.
Measured: Up to 12 months
Time to neurocognitive decline
Measured by Hopkins Verbal Learning Test - Revised (HVLT-R) score. Estimated for each treatment arm using the product limit estimator of Kaplan and Meier. The logrank test stratified by the stratification factors will be used at randomization to compare the 2 treatment arms with respect to the time to neurocognitive decline.
Measured: Up to 12 months
Cumulative incidence of neurocognitive decline
Estimated with death as a competing event.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2012 (estimated)
- Study start2 Aug 2012
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Malignant NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jing Li, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01592968
- Sponsor's protocol ID
- 2011-0884
- Other IDs
- NCI-2014-02058, 2011-0884, NCI-2012-00850
- Status last verified
- Sep 2026
- First submitted
- 3 May 2012
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Phase III Randomized Trial to Compare Stereotactic Radiosurgery vs. Whole Brain Radiation Therapy for >/= 4 Newly Diagnosed Non-Melanoma Brain Metastases
- ClinicalTrials.gov ID
- NCT01592968
- Acronym / sponsor ID
- 2011-0884
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 88 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 2 Aug 2012 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 7 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase III clinical trial compares stereotactic radiosurgery with whole brain radiation therapy to see how well they work in treating patients with non-melanoma cancer that has recently spread from the first location to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic radiosurgery is a specialized type of radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Whole brain radiation therapy delivers a lower dose of radiation to the entire brain over several treatments. It is not yet known whether stereotactic radiosurgery works better than whole brain radiation therapy in treating patients with non-melanoma brain metastases. Stereotactic radiosurgery may also cause fewer thinking and memory problems than whole brain radiation therapy.
Detailed description
PRIMARY OBJECTIVES:
- To compare local tumor control 4 months after treatment of patients with 4 to 15 intracranial non-melanoma metastases at the time of enrollment (=< 15 at time of treatment) treated with stereotactic radiosurgery (SRS) versus (vs.) whole brain radiation therapy (WBRT) in a prospective randomized trial.
II. To compare cognitive decline at 4 months defined as a significant decline (5 point decrease from baseline based on the reliable change index) in Hopkins Verbal Learning Test - Revised (HVLT-R) Total Recall after initial treatment with stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with 4 to 15 non-melanoma brain metastases at the time of enrollment (=< 15 at time of treatment).
SECONDARY OBJECTIVES:
- To determine local control and distant tumor control in the brain at 1, 4, 6, 9, and 12 months post treatment.
II. To determine overall survival in each treatment arm. III. To assess the pattern of neurocognitive change in memory at 1, 4, 6, 9, and 12 months post-treatment as well as executive function, attention, processing speed, and upper extremity fine motor dexterity.
IV. To evaluate the composite neurocognitive function score for both treatment arms.
- To assess the pre-treatment factors of age, Karnofsky performance status (KPS), and extra-cranial disease in the predictive determination of local and distant control and neurocognitive outcome in each treatment arm.
VI. To assess the correlation between number of lesions and total volume of intracranial disease and neurocognitive outcome in each treatment arm.
VII. To compare time to initiation of systemic therapy from completion of radiotherapy between the two treatment arms.
VIII. To compare number of cycles of systemic therapy delivered following completion of radiation treatment in the two treatment arms.
IX. To document and descriptively compare post-treatment adverse side effects between the two treatment arms.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo SRS on day 1.
ARM II: Patients undergo WBRT 5 days per week (7 days per week for inpatients) for 2 weeks.
After completion of study treatment, patients are followed up at 1, 4, 6, 9, and 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (SRS) | Experimental | Other: Cognitive Assessment, Other: Quality-of-Life Assessment, Radiation: Stereotactic RadiosurgeryPatients undergo SRS on day 1. |
| Arm II (WBRT) | Experimental | Other: Cognitive Assessment, Other: Quality-of-Life Assessment, Radiation: Whole-Brain RadiotherapyPatients undergo WBRT 5 days per week (7 days per week for inpatients) for 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- All patients must have greater than 3 but less than or equal to 15 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 up to 20 metastatic lesions at the time of treatment planning (on volumetric MRI once the head frame is in place) may still participate in the trial.
- All patients must be >/= 18 years of age.
- 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.
- 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 .
Key exclusion criteria (7 listed)
- 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).
- Patients will be excluded if they have had prior surgical resection of metastatic cancer from the brain.
- Patients will be excluded if there is radiographic or CSF cytological evidence of leptomenengial disease.
- Patients will be excluded if they have had prior Whole Brain Radiotherapy (WBRT) or prophylactic cranial irradiation (PCI). Prior SRS or Gamma Knife radiosurgery to 1-3 metastases with minimum of (6) weeks to the most recent scan are allowed on protocol.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive AssessmentAncillary studies | Other | Arm I (SRS), Arm II (WBRT) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm I (SRS), Arm II (WBRT) |
| Stereotactic RadiosurgeryAlso: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, stereotactic radiation therapy, Stereotactic RadiotherapyUndergo SRS | Radiation | Arm I (SRS) |
| Whole-Brain RadiotherapyAlso: WBRT, whole-brain radiation therapyUndergo WBRT | Radiation | Arm II (WBRT) |
Primary outcome
Local control rate
Time frame: At 4 months
Estimated for each treatment arm with 95% confidence intervals based on the estimates of time to local failure.
Proportion of patients with neurocognitive decline
Time frame: At 4 months
Defined as a decline of 5 or more points from baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) score. Estimated for each treatment arm with 95% confidence intervals based on the estimates of time to neurocognitive decline.
4 secondary outcomes
Time to local failure
Time frame: Up to 12 months
Cumulative incidence of local failure
Time frame: Up to 12 months
Time to neurocognitive decline
Time frame: Up to 12 months
Cumulative incidence of neurocognitive decline
Time frame: Up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jing Li principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cognitive Assessment, Quality-of-Life Assessment and Stereotactic Radiosurgery in people with Metastatic Malignant Neoplasm and Metastatic Malignant Neoplasm in the Brain, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local control rate (time frame: At 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.