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GRID Therapy for Extremity Soft Tissue Sarcoma

Primary Purpose

Sarcoma

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
GRID therapy
Sponsored by
UNC Lineberger Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring extremity, radiation, GRID, surgery, preoperative

Eligibility Criteria

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

In order to participate in this study a subject must meet all of the eligibility criteria outlined below. Inclusion Criteria: Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information. Subjects are willing and able to comply with study procedures based on the judgment of the investigator. Age ≥ 18 years at the time of consent. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 - 2 (Karnofsky Performance Status equivalent of 50 - 100). Histological or cytological evidence/confirmation of extremity soft tissue sarcoma as determined by core-needle biopsy or excision biopsy. If the diagnostic tissue is not available or sufficient to perform correlative studies, must be willing to provide the mandatory pre-treatment core-needle biopsy. In some cases of extremity STS, subjects undergo an attempted surgical resection for a presumed benign condition and the specimen reveals malignancy. Such subjects are allowed so long as a complete, oncologic, resection was not performed/attempted and there is ≥ 5 cm of the remaining primary tumor. Exclusion Criteria: Subjects meeting any of the exclusion criteria listed below at baseline will be excluded from the study. Subjects who have received prior radiotherapy to the tumor site. Subjects who have undergone complete tumor resection of the primary tumor or who have developed tumor recurrence after resection. History of serious or non-healing wound, ulcer, or bone fracture in the treatment limb within the last 5 years. History of clinically significant lymphedema in the treated limb. History of lupus, scleroderma, Sjogren's syndrome, Ehlers-Danlos syndrome (any type), or other collagen vascular disease that may pose a relative contraindication, due to increased risk of skin or soft tissue toxicity, with radiation.

Sites / Locations

  • University of North Carolina at Chapel Hill, Department of Radiation Oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fractionated grid radiation therapy

Arm Description

Subjects with resectable extremity soft tissue sarcoma received neoadjuvant grid radiation therapy (GRID), followed by standard-of-care conventional radiotherapy (XRT) and tumor resection.

Outcomes

Primary Outcome Measures

Grade 2 or higher post-operative wound complications after GRID-3 months
Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Secondary Outcome Measures

The tumor specimen of the surgery
The effect of GRID on tumor response will be measured using the tumor specimen of the surgery. The major pathological response (MPR) rate will be defined as the viable residual tumor in 10% or less of the resection specimen.
Grade 2 or higher post-operative wound complications after GRID-6 months
Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Long Term Safety
Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
The comparative effect of GRID
The comparative effect of GRID will be quantified using histopathologic substrates. Comparisons will be made between pre-treatment biopsies, biopsies taken from different dose regions of the tumor specimen following GRID, and samples of the surgically resected tumor. The viable tumor rate will be compared.

Full Information

First Posted
September 29, 2023
Last Updated
October 5, 2023
Sponsor
UNC Lineberger Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT06073067
Brief Title
GRID Therapy for Extremity Soft Tissue Sarcoma
Official Title
Safety, Efficacy, and Mechanism of Pre-operative Spatially Fractionated GRID Radiation Therapy in Patients With Extremity Soft Tissue Sarcoma: A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 15, 2023 (Anticipated)
Primary Completion Date
August 15, 2026 (Anticipated)
Study Completion Date
August 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center

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
Patients with extremity soft tissue sarcoma (STS) are at high risk of recurrence. Pre-operative radiotherapy is used to increase the safe removal of tumors and improve local control in these patients. Increasing the preoperative radiotherapy dose with standard techniques might lead to normal tissue toxicity and postoperative wound complications. GRID radiation therapy is a technique that may increases radiation dose with minimal added toxicity. It is hypothesized that GRID radiation dose will improve tumor response without increasing post-operative wound complications. While GRID has been used in many patients, there have been few formal studies to evaluate the safety and efficacy of the technique. In this study, a single priming dose of GRID will be administered to subjects with high-risk extremity soft tissue sarcoma prior to standard radiotherapy and tumor resection to determine the safety and clinical efficacy of the GRID dose. This single-arm pilot study will assess the safety of spatially fractionated grid radiation therapy (GRID) on 20 subjects with resectable extremity soft tissue sarcoma, followed by standard-of-care conventional radiotherapy (XRT) and tumor resection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma
Keywords
extremity, radiation, GRID, surgery, preoperative

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fractionated grid radiation therapy
Arm Type
Experimental
Arm Description
Subjects with resectable extremity soft tissue sarcoma received neoadjuvant grid radiation therapy (GRID), followed by standard-of-care conventional radiotherapy (XRT) and tumor resection.
Intervention Type
Radiation
Intervention Name(s)
GRID therapy
Intervention Description
GRID therapy delivers a high dose of radiation to small areas of tumor interleaved with areas that intentionally receive a low dose
Primary Outcome Measure Information:
Title
Grade 2 or higher post-operative wound complications after GRID-3 months
Description
Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
The tumor specimen of the surgery
Description
The effect of GRID on tumor response will be measured using the tumor specimen of the surgery. The major pathological response (MPR) rate will be defined as the viable residual tumor in 10% or less of the resection specimen.
Time Frame
At the time of surgery (Approximately 17th week)
Title
Grade 2 or higher post-operative wound complications after GRID-6 months
Description
Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time Frame
3 months to 6 months
Title
Long Term Safety
Description
Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time Frame
6 months after completrion of radiotherapy
Title
The comparative effect of GRID
Description
The comparative effect of GRID will be quantified using histopathologic substrates. Comparisons will be made between pre-treatment biopsies, biopsies taken from different dose regions of the tumor specimen following GRID, and samples of the surgically resected tumor. The viable tumor rate will be compared.
Time Frame
At the time of surgery (Approximately 17th week after completion of radiotherapy)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
In order to participate in this study a subject must meet all of the eligibility criteria outlined below. Inclusion Criteria: Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information. Subjects are willing and able to comply with study procedures based on the judgment of the investigator. Age ≥ 18 years at the time of consent. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 - 2 (Karnofsky Performance Status equivalent of 50 - 100). Histological or cytological evidence/confirmation of extremity soft tissue sarcoma as determined by core-needle biopsy or excision biopsy. If the diagnostic tissue is not available or sufficient to perform correlative studies, must be willing to provide the mandatory pre-treatment core-needle biopsy. In some cases of extremity STS, subjects undergo an attempted surgical resection for a presumed benign condition and the specimen reveals malignancy. Such subjects are allowed so long as a complete, oncologic, resection was not performed/attempted and there is ≥ 5 cm of the remaining primary tumor. Exclusion Criteria: Subjects meeting any of the exclusion criteria listed below at baseline will be excluded from the study. Subjects who have received prior radiotherapy to the tumor site. Subjects who have undergone complete tumor resection of the primary tumor or who have developed tumor recurrence after resection. History of serious or non-healing wound, ulcer, or bone fracture in the treatment limb within the last 5 years. History of clinically significant lymphedema in the treated limb. History of lupus, scleroderma, Sjogren's syndrome, Ehlers-Danlos syndrome (any type), or other collagen vascular disease that may pose a relative contraindication, due to increased risk of skin or soft tissue toxicity, with radiation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Flora Danquah
Phone
919-843-5400
Email
flora_danquah@med.unc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Claire Kowalczyk
Email
claire_kowalczyk@med.unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Theodore K Yanagihara, MD. PhD
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill, Department of Radiation Oncology
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

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GRID Therapy for Extremity Soft Tissue Sarcoma

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