Brain Metastases
Conditions
Brief summary
This pilot study is a randomized, open-label, 2-arm active-controlled phase II clinical trial conducted at a single study site (UAMS). Subjects will be randomized to one of the 2 treatment arms and stratified by size of index lesion and number of brain metastases. The investigators will prospectively compare preoperative (neoadjuvant) SRS/SRT to postoperative (adjuvant) SRS/SRT in patients undergoing surgical resection for brain metastases. The investigators hypothesize that neoadjuvant SRS/SRT prior to surgical resection of brain metastases will result in improved freedom from Central Nervous System (CNS) events when compared to adjuvant SRS/SRT after surgical resection.
Interventions
RADIATIONSRS/SRT
Comparing pre-operative SRS/SRT to post-operative SRS/SRT
Sponsors
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with prior histopathological diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell histologies. * MR imaging of the brain with findings strongly suggestive of metastatic tumor(s) as assessed by the radiologist. * Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate both surgery and SRS/SRT, e.g., the ability to lie flat in a stereotactic soft head frame. * ECOG ≤ 2 * 1-2 index lesion(s) appropriate for resection, not previously treated with SRS/SRT. Index lesion(s) should be \> 2 cm and \< 5 cm in largest dimension, and require resection. Alternatively, patients with a diagnosis of melanoma and a lesion \< 1.5cm in largest dimension may also be included. o All other brain lesions must be appropriate for SRS/SRT alone and treated according to physician preference. Prior neurosurgery and/or prior SRS/SRT at a non-overlapping location are permitted at the discretion of the treating physician. \- MRI confirmed 1-10 lesions, 1-2 of which are the index lesions undergoing surgery. Each non-index lesion (up to 10) must measure ≤ 3.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection. * Clinical indication and plan for stereotactic radiosurgery to all known brain lesions requiring treatment (≤ 10 metastases). * Surgical resection able to be performed within 15 days of radiotherapy completion. * Written informed consent obtained from subject, or a legally designated power of attorney and ability for subject to comply with the requirements of the study. * Negative pregnancy test in women of childbearing potential (WOCBP) within 30 days of radiation. WOCBP is a female patient less than 50 years of age or who has menstruated within the last 12 months. * Platelet count \> 80 k/cumm, Hgb \> 7.5 gm/dL, INR \< 1.3, ANC \> 1.5 k/cumm
Exclusion criteria
* Not a surgical candidate per neurosurgeon's discretion. * Contraindication to general anesthesia. * Not a radiosurgical candidate per radiation oncologist's discretion. * Metastatic germ cell tumor, small cell carcinoma, leukemia, multiple myeloma or lymphoma or any primary brain tumor * ECOG \> 2 * \< 3 months expected survival * Radiologic documentation of hydrocephalus in addition to symptoms of hydrocephalus * Radiographic or cytologic evidence of leptomeningeal disease. * Imaging Findings: * Midline shift \> 6mm * \>10 lesions, one of which is the index lesion * Largest lesion \> 5cm * Pregnancy * Known allergy to gadolinium, pacemaker, or other contraindication such as metal implant that is not safe for MRI. Patients with MRI-compatible implants are eligible. * Patients who have local recurrence of previously treated brain metastasis. * Patients who have received prior WBRT. * Inherited radiation hypersensitivity syndromes o Ataxia Telangiectasia, Nijmegen Breakage Syndrome, Fanconi Anemia, DNA Ligase IV, Mre 11 deficiency, SCID, Bloom's syndrome * Collagen vascular diseases o Active systemic lupus erythematous (SLE), scleroderma, mixed connective tissue disorder, polymyositis or dermatomyositis, CREST Syndrome * Cytotoxic Chemotherapy within 7 days prior to SRS/SRT. o Molecularly targeted therapies, including immune-modulatory drugs, can be given within 7 days of SRS/SRT at the discretion of the treating physician. * Patients who received anti-VEGF therapy within 6 weeks prior to enrollment, as there is increased risk of fatal brain hemorrhage with surgical resection. * Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Central Nervous System (CNS) Composite Event (CE) | From date of randomization to the date of a documented LR, SRN, or LMD, whichever comes first, assessed up to 18 months. | A CNS CE will consist of one of the following three events: Local Recurrence (LR) of the treated lesions, symptomatic radiation necrosis (SRN) to the treated lesions, or development of leptomeningeal disease (LMD). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Pre-operative SRS/SRT) Patients undergo SRS or SRT within 15 days of randomization followed by surgery within 15 days of radiation completion. Patients may undergo additional SRS or SRT if disease returns after treatment.
SRS/SRT: Comparing pre-operative SRS/SRT to post-operative SRS/SRT | 1 |
| Arm II (Post-operative SRS/SRT) Patients undergo surgery within 15 days of randomization followed by standard-of-care SRS or SRT within 30 days of surgery. Patients may undergo additional SRS or SRT if disease returns after treatment.
SRS/SRT: Comparing pre-operative SRS/SRT to post-operative SRS/SRT | 2 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | study closed prior to completion of FU visits | 0 | 2 |
Baseline characteristics
| Characteristic | Arm II (Post-operative SRS/SRT) | Total | Arm I (Pre-operative SRS/SRT) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 1 / 2 |
Outcome results
Primary
Number of Participants With Central Nervous System (CNS) Composite Event (CE)
A CNS CE will consist of one of the following three events: Local Recurrence (LR) of the treated lesions, symptomatic radiation necrosis (SRN) to the treated lesions, or development of leptomeningeal disease (LMD).
Time frame: From date of randomization to the date of a documented LR, SRN, or LMD, whichever comes first, assessed up to 18 months.
Population: No data displayed because Outcome Measure has zero total participants analyzed due to low enrollment and early study termination. Study closed prior to completion of follow-up visits so there is nothing to analyze.