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

Primary Purpose

Brain Metastases

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
intraoperative radiotherapy (IORT)
Sponsored by
University of Louisville
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Louisville, James Graham Brown Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

intraoperative radiotherapy (IORT) arm

Outcomes

Primary Outcome Measures

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.
Number of Participants With Adverse Events
Number of adverse events reported per participant.

Secondary Outcome Measures

Full Information

First Posted
July 20, 2019
Last Updated
October 10, 2023
Sponsor
University of Louisville
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1. Study Identification

Unique Protocol Identification Number
NCT04040400
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
per DMSC request
Study Start Date
October 23, 2019 (Actual)
Primary Completion Date
November 19, 2021 (Actual)
Study Completion Date
November 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Louisville

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
intraoperative radiotherapy (IORT) arm
Intervention Type
Radiation
Intervention Name(s)
intraoperative radiotherapy (IORT)
Intervention Description
intraoperative radiotherapy (IORT) during brain tumor resection to establish a maximum tolerated dose (MTD) through a dose-escalation trial using intraoperative radiotherapy (IORT)
Primary Outcome Measure Information:
Title
Established Maximum Tolerated Dose
Description
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.
Time Frame
Phase I cohorts; 90 days from treatments
Title
Number of Participants With Adverse Events
Description
Number of adverse events reported per participant.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shaio Woo, MD
Organizational Affiliation
University of Louisville, JGBrown Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville, James Graham Brown Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No plans to share individual participant data with other researchers outside of this clinical trial's investigation team

Learn more about this trial

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

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