Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection

Not Applicable

Terminated

Conditions: Brain Metastases

Interventions: Radiation: intraoperative radiotherapy (IORT)

Registration Number: NCT04040400

Lead Sponsor: University of Louisville

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Participants must be ≥ 18 years of age.
Participants must have a Karnosfky performance status of ≥ 50%.
Participants must not have had prior intracranial radiation.
Participants must have a life expectancy greater than 3 months.
Participants must have a preoperative MRI Brain T1-Gadolinum enhanced scan demonstrating a non-dural based lesion with greatest diameter ≥ 2.5 cm.
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.
Subject or subject's legal representative to provide signed/written informed consent to participate in the study protocol.
Surface of balloon applicator must be ≥ 1cm from skin overlying closest portion of calvarium.
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

Participants may not be pregnant or breast-feeding.
Patients must not have dural lesions or leptomeningeal disease.
Patients must not have psychiatric or social conditions limiting adherence to protocol guidelines.
Patients must not have contraindications to anesthesia, surgery, or MR imaging with Gadolinium injection.
Patients must not have a frozen section diagnosis of small cell carcinoma, lymphoma, germinoma or non-malignant histology.
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.
Patients deemed to require postoperative whole brain radiotherapy should be excluded.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	intraoperative radiotherapy (IORT)	intraoperative radiotherapy (IORT) arm

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	12 months	Number of adverse events reported per participant.
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.