Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection
Study Details
Study Description
Brief Summary
The primary purpose of this study is to establish a maximum tolerated dose (MTD) through a dose-escalation trial using intraoperative radiotherapy (IORT) following neurosurgical resection for large brain metastases, and to determine the progression-free survival rate as in the recurrence rate of treated brain metastasis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The potential for delivering ablative doses of radiation to the tumor bed while simultaneously sparing normal brain parenchyma from significant doses of radiation and reducing the potential for tumor repopulation has led to interest in the use of intraoperative radiotherapy (IORT) for brain metastasis.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm intraoperative radiotherapy (IORT) arm |
Device: intraoperative radiotherapy (IORT)
intraoperative radiotherapy (IORT) during brain tumor resection
|
Outcome Measures
Primary Outcome Measures
- Established Maximum tolerated dose [Phase I cohorts; 90 days from treatments]
Maximum tolerated dose will be determined by classical 3+3 dose-escalation design. Toxicity will be measured using the National Cancer Institute Common terminology criteria for adverse events (version 5.0). The first dose of 18Gy will be administered to the first 3 subjects, after 90 days from treatment a safety assessment for dose limiting toxicities will be done to determine if the next 3 subject will escalation to dose of 21Gy or receive 18Gy. If escalation to 21Gy is permitted, then after 90 days from treatment a safety assessment for dose limiting toxicities will be done to determine if next cohort of 3 subjects will escalate to a dose of 24Gy or receive 21Gy. The highest dose level to be administered will be 24 Gy if permitted by safety assessments.
- Final Overall survival [through study completion, an average of 10 years]
Kaplan-Meier methods and the log-rank test will be used to estimate survival outcomes including overall survival.
- Recurrence rate of treated brain metastasis [through study completion, an average of 10 years]
Multivariable Cox regression will be used to evaluate prognostic factors associated with survival.
Secondary Outcome Measures
- Functional Assessment of Cancer Therapy-Brain (FACT-Br) [through study completion, an average of 10 years]
The Questionnaire Functional Assessment of Cancer Therapy (FACT) is a self-reported quality of life questionnaire that includes 27 items. The brain tumor specific version, is an additional 23-item sub-scale set of disease-specific questions pertaining to brain neoplasms. Patients rate each question using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Item areas are: physical well-being, social/family well-being, emotional well-being, functional well-being and sub-scale item area relevant to patients with brain tumors. Overall, higher ratings suggest higher Quality of Life score. Items are totaled (summed) to produce the following subscales, along with an overall QOL score: physical well-being (7 items); social/family well-being (7 items); emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participants must be ≥ 18 years of age.
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Participants must have a Karnosfky performance status of ≥ 50%.
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Participants must not have had prior intracranial radiation.
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Participants must have a life expectancy greater than 3 months.
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Participants must have a preoperative MRI Brain T1-Gadolinum enhanced scan demonstrating a non-dural based lesion with greatest diameter ≥ 2.5 cm.
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Sufficient distance (≥ 2cm) of the intracranial lesion from optic structures (optic chiasm and bilateral optic nerves) and brainstem to meet established normal structure dose limits.
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Subject or subject's legal representative to provide signed/written informed consent to participate in the study protocol.
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Surface of balloon applicator must be ≥ 1cm from skin overlying closest portion of calvarium.
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Participants may remain on systemic therapy if they are receiving immunotherapy (anti-PD1, anti-PDL1, anti-CTLA-4), capecitabine, temozolomide, etoposide, vinorelbine, pemetrexed, lapatinib, traztuzumab, bevacizumab, mTor or ALK targeted agents with no break prior to initiating IORT.
9.1 Participants receiving cisplatin, methotrexate, taxanes, tyrosine kinase inhibitors, or BRAF targeted agents must have a seven day washout period prior to receiving IORT.
9.2 Participants receiving doxorubicin, T-DM1, or antibody-drug conjugates must have a fourteen day washout period prior to receiving IORT.
9.3. Participants receiving all other concurrent systemic agents will undergo consideration for a washout period prior to receiving IORT at the discretion of the study principal investigator.
Exclusion Criteria:
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Participants may not be pregnant or breast-feeding.
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Patients must not have dural lesions or leptomeningeal disease.
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Patients must not have psychiatric or social conditions limiting adherence to protocol guidelines.
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Patients must not have contraindications to anesthesia, surgery, or MR imaging with Gadolinium injection.
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Patients must not have a frozen section diagnosis of small cell carcinoma, lymphoma, germinoma or non-malignant histology.
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Patients with additional unresected brain metastases must have a limited number of lesions/or volume of intracranial disease amenable to stereotactic radiotherapy at the discretion of the study principal investigator.
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Patients deemed to require postoperative whole brain radiotherapy should be excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Louisville, James Graham Brown Cancer Center | Louisville | Kentucky | United States | 40202 |
Sponsors and Collaborators
- University of Louisville
Investigators
- Principal Investigator: Shaio Woo, MD, University of Louisville, JGBrown Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19.0619 BCC-IORT-BM