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

NCT04040400 | Terminated Results DMC FDA Device

• 1 other identifier: 19.0619 BCC-IORT-BM
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastases

Outcome Measures

Primary Outcomes (2)

• Established Maximum Tolerated Dose

  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.

  Phase I cohorts; 90 days from treatments

• Number of Participants With Adverse Events

  Number of adverse events reported per participant.

  12 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

intraoperative radiotherapy (IORT) arm

Radiation: intraoperative radiotherapy (IORT)

Interventions

intraoperative radiotherapy (IORT) RADIATION

intraoperative radiotherapy (IORT) during brain tumor resection to establish a maximum tolerated dose (MTD) through a dose-escalation trial using intraoperative radiotherapy (IORT)

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Participants receiving cisplatin, methotrexate, taxanes, tyrosine kinase inhibitors, or BRAF targeted agents must have a seven day washout period prior to receiving IORT.
• Participants receiving doxorubicin, T-DM1, or antibody-drug conjugates must have a fourteen day washout period prior to receiving IORT.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Louisville: lead

Study Sites (1)

University of Louisville, James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Shiao Woo, MD Principal Investigator
• Organization: University of Louisville Brown Cancer Center

shiao.woo@louisville.edu

502-562-4360

Study Officials

• Shaio Woo, MD

  University of Louisville, JGBrown Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: July 20, 2019
• First Posted: July 31, 2019
• Study Start: October 23, 2019
• Primary Completion: November 19, 2021
• Study Completion: November 19, 2021
• Last Updated: October 12, 2023
• Results First Posted: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)