Clinical trial NCT04040400: Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection
Official title: A Phase I/II Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Brain Metastases
Lead sponsor: University of Louisville
Sponsor class: OTHER
First posted: 2019-07-31
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The resection procedure should be performed with image guidance (neuronavigation) with standard surgical technique.

Optimal balloon applicator size will be selected with accordance to tumor bed/cavity geometry and adjacent normal brain parenchyma by the team of surgeons and radiation oncologists.

The radiation oncologist will place the miniature x-ray source inside the balloon shaped catheter placed inside the tumor cavity. Radiotherapy will be initiated by the treating radiation oncologist for a defined time interval calculated by the machine planning software.

After IORT has been delivered, the surgeon will remove the balloon applicator. Surgery will be continued in the regular fashion without additional requirements.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Participants must be ≥ 18 years of age.
2. Participants must have a Karnosfky performance status of ≥ 50%.
3. Participants must not have had prior intracranial radiation.
4. Participants must have a life expectancy greater than 3 months.
5. Participants must have a preoperative MRI Brain T1-Gadolinum enhanced scan demonstrating a non-dural based lesion with greatest diameter ≥ 2.5 cm.
6. 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.
7. Subject or subject's legal representative to provide signed/written informed consent to participate in the study protocol.
8. Surface of balloon applicator must be ≥ 1cm from skin overlying closest portion of calvarium.
9. 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:

1. Participants may not be pregnant or breast-feeding.
2. Patients must not have dural lesions or leptomeningeal disease.
3. Patients must not have psychiatric or social conditions limiting adherence to protocol guidelines.
4. Patients must not have contraindications to anesthesia, surgery, or MR imaging with Gadolinium injection.
5. Patients must not have a frozen section diagnosis of small cell carcinoma, lymphoma, germinoma or non-malignant histology.
6. 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.
7. Patients deemed to require postoperative whole brain radiotherapy should be excluded.

Primary outcomes:
measure: Established Maximum Tolerated Dose
timeFrame: Phase I cohorts; 90 days from treatments
measure: Number of Participants With Adverse Events
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville, James Graham Brown Cancer Center
state: Kentucky
Study officials:
affiliation: University of Louisville, JGBrown Cancer Center
name: Shaio Woo, MD
role: PRINCIPAL_INVESTIGATOR
References: