Brain Metastases
Conditions
Brief summary
This is a prospective, single arm, phase II trial to determine the local control at 6 months utilizing pre-operative stereotactic radiosurgery followed by surgery within 1 - 4 days in subjects with a diagnosis of 1-4 brain metastases and with an indication for surgical resection of at least one brain metastasis at the discretion of a neurosurgeon.
Detailed description
Primary Objective To evaluate 6 month in-brain local control utilizing pre-operative stereotactic radiosurgery followed by surgical resection for brain metastases. Secondary Objectives * Overall survival * Distant in-brain progression * Rate of leptomeningeal spread * Rate of radiation necrosis
Interventions
PROCEDURERadiosurgery
Stereotactic radiosurgery will be delivered on all patients utilizing gamma knife or linear accelerator based techniques as per RTOG-9005 dosing criteria (Section 11 Table 1) based on tumor diameter with the exception that the largest lesion diameter to be treated with 15 Gy will be 5 cm. All apparent, previously untreated brain metastases will be treated with radiosurgery at this time. Radiosurgery will be performed 1-4 days prior to surgical resection. Vital signs and MRI Brain planning scan will be performed on the day of radiosurgery prior to the procedure.
Sponsors
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Radiographically confirmed solid tumor brain metastases 2. Criteria for surgical resection of at least one metastasis per neurosurgeon discretion 3. A diagnostic MRI Brain or CT Head demonstrating the presence of 1-4 solid tumor brain metastases and lesion to be resected no more than 5 cm in any direction, performed within 30 days prior to stereotactic radiosurgery. If multiple lesions are present, then the total brain metastases volume can be no more than 30 cm3 excluding the lesion to be resected. 4. For known primary included in brainmetgpa.com, an estimated median survival no less than 6 months per brainmetgpa.com 5. For unknown primary or known primary not included within brainmetgpa.com, an estimated median survival no less than 6 months per PI discretion Note: If patient's estimated median survival is calculated using a histology that is different than the histology demonstrated in final pathology, the patient may remain eligible for all study endpoints per PI discretion 6. Surgical candidate per neurosurgeon discretion 7. Surgical resection able to be performed within 1 - 4 days after radiosurgery 8. Stereotactic radiosurgery candidate per radiation oncologist 9. ≥ 18 years old at the time of informed consent 10. Ability to provide written informed consent and HIPAA authorization. This will be assessed by the consenting physician using general questions to determine the patient's ability to understand the medical problem, proposed treatment, alternatives to proposed treatment, and understand the consequences of the medical choices. 11. Platelet count \> 100 k/cumm, Hgb \> 7.5 gm/dL, INR \< 1.3, ANC \> 1.5 k/cumm 12. Patients currently on cytotoxic chemotherapy or immunotherapy are eligible, not including anti-VEGF therapy 13. If a patient who meets all stated eligibility criteria is enrolled on study and then discovered to be ineligible, the tissue obtained will still be deemed eligible to remain in study for evaluation.
Exclusion criteria
1. Patients who received anti-VEGF therapy within 6 weeks prior to enrollment, as there is increased risk of fatal brain hemorrhage with surgical resection 2. Major medical illnesses or psychiatric impairments, which in the investigator's opinion will prevent administration or completion of the protocol therapy and/or interfere with follow-up 3. Patients with more than 4 brain metastases on MRI Brain or CT Head 4. Lesion to be resected is more than 5 cm 5. Total volume of metastatic disease more than 30 cm3 excluding lesion to be resected 6. Patients with leptomeningeal metastases documented by MRI or CSF evaluation 7. Previous whole brain radiation therapy 8. Previous radiation therapy to lesion to be resected 9. Planned adjuvant focal therapy including additional radiation therapy to the brain 10. Not a surgical candidate per neurosurgeon's discretion 11. Not a radiosurgical candidate per radiation oncologist's discretion 12. Surgery unable to be performed between 1 - 4 days after radiosurgery 13. Women who are pregnant or nursing are not eligible as treatment involves unforeseeable risks to the fetus or child
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of local control of any new, recurrent, or progressing tumors within the planning target volume | 6 months | Measured by post-treatment MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of overall survival | 6 months, 1 year, and 2 years | Time from start of treatment to death of any cause |
| Rate of in-brain progression free survival | 6 months, 1 year, and 2 years | Time from start of treatment to any in-brain |
| Proportion of patients with radiation necrosis (radiographic or biopsy-positive diagnosis of radiation necrosis) | 2 years | Measured by post-treatment MRI |
| Proportion of patients with leptomeningeal spread (radiographic or CSF diagnosis of leptomeningeal disease) | 2 years | Measured by post-treatment MRI |
| Proportion of patients with distant in-brain failure (any new parenchymal lesion outside of the planning target volume) | 2 years | Measured by post-treatment MRI |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory: Correlation of RNA biomarkers | 2 yrs | Correlation of RNA biomarkers with local control |
Countries
United States
Outcome results
None listed