Radiosurgery With or Without Whole Brain Radiation for Multiple Metastases
- Conditions
- Brain Metastases
- Interventions
- Radiation: Stereotactic Radiosurgery (SRS)Radiation: Whole brain radiation (WBRT)
- Registration Number
- NCT03775330
- Lead Sponsor
- Sunnybrook Health Sciences Centre
- Brief Summary
This clinical study is a parallel, prospective observational single-centre trial in patients presenting with 5 to 30 brain metastases. Patients to receive either stereotactic radiosurgery (SRS) alone or SRS plus whole brain radiation (WBRT) will be enrolled.
- Detailed Description
The current standard of care for patients with limited brain metastases (1 to 4) is stereotactic radiosurgery (SRS) alone. This has evolved from the traditional standard of care in treating patients with whole brain radiation (WBRT). Studies in patients with limited (less than 5) brain metastases have shown that WBRT is harmful with respect to neurocognition and does not improve patient survival compared to SRS alone. As a result, SRS alone now is considered the standard of care treatment for patients with limited metastases. However, there is a lack of high quality prospective randomized evidence on the role of SRS in patients with 5 or more brain metastases to guide treatment.
Therefore, this study seeks to prospectively compare SRS alone versus SRS plus WBRT in patients with 5 to 30 brain metastases.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 126
- Histologic or cytologic diagnosis of non-hematopoietic malignancy (excluding germ cell malignancies and small cell carcinoma).
- Patients with ≥ 5 but ≤ 30 de novo brain metastases seen on a diagnostic-quality contrast-enhanced MRI obtained within 30 days prior to enrollment (or randomization if previously randomized). Patients who are found to have 31-50 metastatic lesions at the time of treatment planning may still participate in the study. Disease progression such that > 50 brain metastases are detected after initial MRI prior to enrollment but before SRS will be treated off-protocol as per discretion of the treating physician.
- Patients with ≥ 5 but ≤ 30 new brain metastases who have undergone prior SRS for 4 or less brain metastases with stable intracranial disease as per diagnostic MRI for at least 6 months post last course of SRS. Patients who are found to have 31-50 new metastatic lesions at the time of treatment planning may still participate in the study. Disease progression such that > 50 new brain metastases are detected after initial MRI prior to enrollment but before SRS will be treated off-protocol as per discretion of the treating physician.
- Age ≥ 18.
- Karnofsky Performance Status (KPS) ≥ 70.
- Baseline HVLT-R above ≥ 6
- Patients must be able to tolerate WBRT, and all brain lesions must be eligible for treatment with SRS as determined by the radiation oncologist.
- Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
- Patient is able to read, speak, and understand (i.e. sufficiently fluent) English in order to allow completion and meaningful analyses of the neurocognitive tests and quality of life questionnaires.
- Patients must be accessible for treatment and follow up. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
- Patients who are on immunotherapy must have immunotherapy held at least 1 week before and after completion of radiotherapy. Other targeted agents/therapy must be held at least 1 day before and after SRS. Systemic chemotherapy must be held one week prior to treatment and re-started one week after treatment is complete.
- Protocol treatment is to begin within 4 weeks of patient enrollment (or randomization if previously randomized).
- Patients with brain metastases resulting from germ cell malignancies, small cell carcinoma, or hematologic malignancies.
- Prior SRS for 5 or more brain metastases or any SRS for brain metastases within the last 6 months.
- Any prior WBRT or radiotherapy for brain metastases such that the study interventions cannot be delivered.
- Prior surgical resection of metastatic cancer from the brain.
- Patients with evidence of leptomeningeal disease.
- Patients who have a pacemaker or other contraindications, such that gadolinium-enhanced MRI cannot be performed or treatment cannot be delivered safely.
- Patients who have received chemotherapy or immunotherapy within 1 week prior to administration of protocol radiotherapy or who are expected / planned to receive chemotherapy within one week of completing protocol radiotherapy.
- Patients with < 5 or > 30 de novo or new brain metastases at time of enrollment, or > 50 brain metastases at time of treatment planning.
- Patients who are pregnant (women of child-bearing age must have negative pregnancy urine test within 7 days of enrollment or randomization).
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description SRS plus WBRT Whole brain radiation (WBRT) Stereotactic radiosurgery plus whole brain radiation SRS Stereotactic Radiosurgery (SRS) Stereotactic radiosurgery SRS plus WBRT Stereotactic Radiosurgery (SRS) Stereotactic radiosurgery plus whole brain radiation
- Primary Outcome Measures
Name Time Method Neurocognitive function 2 months post treatment Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI)
- Secondary Outcome Measures
Name Time Method Local control of sites initially treated by SRS 2 months, 4 months, 6 months, and 9 months Defined by the response criteria stipulated in the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria guideline
Overall central nervous system (CNS) response 2 months, 4 months, 6 months, and 9 months Response will be recorded for each individual target lesion and for overall central nervous system (CNS) response as a composite of radiographical CNS target and non-target lesion responses, corticosteroid use, and clinical status defined as per RANO-BM criteria
Neurocognitive function - Trail Making Test 2 months, 4 months, 6 months, and 9 months Trail Making Test (TMT, Part A and Part B)
Neurocognitive function - Clinical Trial Battery Composite 2 months, 4 months, 6 months, and 9 months Clinical Trial Battery Composite (CTB COMP) score
Neurocognitive function - HVLT-R 2 months, 4 months, 6 months, and 9 months Hopkins Verbal Learning Test-Revised (HVLT-R) (Total Recall, Delayed Recall, Delayed Recognition)
Neurocognitive function - Controlled Oral Word Association 2 months, 4 months, 6 months, and 9 months Controlled Oral Word Association (COWA)
Distant tumour control within the brain 2 months, 4 months, 6 months, and 9 months Distant brain failure is defined as the appearance of one or more new lesions on a diagnostic-quality, contrast-enhanced MRI within the brain at sites other than those initially treated by SRS
Overall survival From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months Response recorded for survival
Measure of Quality of Life 2 months, 4 months, 6 months, and 9 months Health-Related QoL as measured by Functional Assessment of Cancer Therapy - Brain (FACT-Br) instrument
Incidence of Brain Salvage therapy During Follow-up 2 months, 4 months, 6 months, and 9 months Number/proportion of patients requiring salvage therapy and type of salvage therapy, for progressive intracranial disease during follow-up
Trial Locations
- Locations (1)
Sunnybrook Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada