Back to resultsA Phase II Trial of Preoperative Proton Therapy in Soft-tissue Sarcomas of the Extremities and Body Wall
Primary Purpose
Soft Tissue Sarcoma
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
proton radiation
surgery (wide local excision; limb preservation surgery)
Sponsored by
About this trial
This is an interventional treatment trial for Soft Tissue Sarcoma focused on measuring extremity soft tissue sarcoma, proton radiation, preoperative radiation
Eligibility Criteria
Inclusion Criteria:
- Histologically proven primary soft tissue sarcoma of the upper extremity (including shoulder), lower extremity (including hip) or body trunk (excluding retroperitoneum).
- No clinical evidence of distant metastatic disease
- Evaluation by surgeon, with documentation that the tumor is resectable
- ECOG performance status 0-1
- For females of childbearing potential, a serum pregnancy test within 4 weeks prior to registration
- Patient must practice adequate contraception
- Adequate bone marrow function
Exclusion Criteria:
- Patients with sarcoma of the head, neck, intra-abdominal or retroperitoneal region, hand or foot
- Histopathology demonstrating rhabdomyosarcoma, extraosseous primitive neuroectodermal tumor (PNET), soft tissue Ewing's sarcoma, osteosarcoma, Kaposi's sarcoma, angiosarcoma, aggressive fibromatosis, dermatofibrosarcoma protuberans or chondrosarcoma
- Clinical evidence of regional lymph node or distant metastatic disease
- Prior invasive malignancy (except non-melanomatous skin cancer or early stage prostate cancer) unless disease free for a minimum of 3 years
- Prior radiotherapy to the potential target anatomic region would result in overlap of radiation fields for current sarcoma
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to used medically acceptable forms of contraception
Sites / Locations
- Loma Linda University Medical Center / James M. Slater Proton Treatment Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Preoperative proton radiation
Arm Description
Patients will receive 50 Gray equivalents (GyE) in 25 fractions with proton therapy, followed by surgery 4-8 weeks after completion of radiation.
Outcomes
Primary Outcome Measures
Late Radiation Toxicities at 2 Years From the Start of Radiation Treatment
To report the number of participants with late radiation morbidity
Late subcutaneous fibrosis and joint stiffness are assessed using the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) late toxicity scoring criteria below:
Subcutaneous tissue: Grade 1(slight fibrosis; subcutaneous fat loss), Grade 2(moderate fibrosis: slight field contracture), Grade 3(severe fibrosis; field contracture >10%), Grade 4(necrosis), Grade 0 (none) Joint stiffness: Grade 1(mild stiffness; slight range of motion loss), Grade 2(Moderate stiffness, pain, range of motion loss), Grade 3(Severe stiffness, pain, range of motion loss), Grade 4(necrosis; complete fixation), Grade 0 (none) Lymphedema is measured according to the criteria of Stern: Score 0(none), Score 1(Mild but definite swelling), Score 2(Moderate), Score 3(Severe, considerable swelling), Grade 4(Very severe (skin shiny & tight)
Secondary Outcome Measures
Grade 3-5 Adverse Events at 6 Months From the Start of Radiation Treatment.
This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for reporting of adverse events.
Patterns of Failure at 6 Months From the Start of Radiation Treatment
Prespecified patterns of failure, including local failure, regional failure, distant failure, and death without disease progression at 6 months from the start of radiation treatment measured by CT or MRI scan
Patterns of Failure at 6 Months
Patterns of failure including local failure, distant failure, distant-disease-free survival, disease-free survival, overall survival rates, and second primary tumor at 6 month from the start of radiation treatment on CT or MRI scan.
Wound Complication Rates Infection, Dehiscence at 6 Months From the Start of Radiation Treatment.
Wound complications - Major wound complications, such as secondary operations, re-admissions, and/or invasive procedures for wound complication (deep wound packing and/or prolonged dressing changes) due to Infection, dehiscence.
Report of Late Radiation Morbidity at 2 Years
To report the number of participants with late radiation morbidity using quality of life survey including physical, emotional, social/family and functional well-being.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01819831
Brief Title
A Phase II Trial of Preoperative Proton Therapy in Soft-tissue Sarcomas of the Extremities and Body Wall
Official Title
A Phase II Trial of Preoperative Proton Therapy in Soft-tissue Sarcomas of the Extremities and Body Wall
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
February 27, 2013 (Actual)
Primary Completion Date
May 19, 2022 (Actual)
Study Completion Date
May 19, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Loma Linda University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
When treated with surgery alone, many soft-tissue sarcomas have a high chance of coming back. Radiation therapy is frequently used in addition to surgery to reduce the chances of the sarcoma coming back. However, radiation can have long-term side effects on the normal tissues surrounding the tumor, leading to problems such as swelling, scarring, and joint stiffness.
Recently, there have been advances in the way that radiation therapy can be given. Proton radiation therapy is one of those advances. With proton radiation, it is possible to give radiation over a smaller area surrounding the tumor, resulting in less radiation to the surrounding normal tissues.
The purpose of this study is to determine whether proton radiation decreases the long-term side effects of radiation on normal tissues and if smaller proton radiation fields reduce local recurrence compared to the larger radiation fields that have been used in prior studies.
Detailed Description
Data support preoperative radiotherapy as one of the standard options in the management of large or high-grade extremity soft tissue sarcomas (STS). The advantages of preoperative radiotherapy are lower doses and smaller radiation volumes; these may be used to effect improvement of long-term side effects and extremity function. Another potential advantage is assisting surgery through tumor shrinkage and reduction of tumor cell seeding. The disadvantage of preoperative radiation is the higher likelihood of postoperative wound complications, but in a prospective phase III trial these complications were found to be generally temporary and without significant effect on long term function.
Combined conservative surgery and radiotherapy has shown to achieve excellent local control in sarcoma patients following margin-negative surgery, but late radiation morbidity and reduced quality of life may result from adjuvant radiation. The dosimetric advantage of proton radiotherapy may translate into reduced acute and late effects due to improved normal-tissue sparing in the treatment of extremity and truncal STS. However, these potential advantages need to be validated in clinical trials. The investigators propose a phase II study to evaluate the effect of preoperative proton radiotherapy on the reduction of late radiation morbidity, patterns of failure, and impact of late radiation morbidity on general quality of life (QOL).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma
Keywords
extremity soft tissue sarcoma, proton radiation, preoperative radiation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Preoperative proton radiation
Arm Type
Experimental
Arm Description
Patients will receive 50 Gray equivalents (GyE) in 25 fractions with proton therapy, followed by surgery 4-8 weeks after completion of radiation.
Intervention Type
Radiation
Intervention Name(s)
proton radiation
Other Intervention Name(s)
Proton radiotherapy, Proton treatment
Intervention Description
proton radiation: 2 GyE/Day to isocenter, one treatment per day, 5 days per week for 25 treatments (=50 GyE to isocenter/25 fractions)
Intervention Type
Procedure
Intervention Name(s)
surgery (wide local excision; limb preservation surgery)
Other Intervention Name(s)
wide local excision, limb preservation surgery
Intervention Description
In areas with ample soft tissue that can be removed without compromising future function or wound closure, wide margins is the goal of treatment; associated rates of local failure are low in such instances. Margins will be determined by the surgeon; the goal is to achieve at least a 2 mm negative margin resection. However, smaller margins can be acceptable if it allows for limb-sparing surgery with conserved functional outcomes. Every effort will be made to have limb preservation surgery unless there is documented evidence of tumor progression during or after the course of radiation that would require amputation for an appropriate margin resection.
Primary Outcome Measure Information:
Title
Late Radiation Toxicities at 2 Years From the Start of Radiation Treatment
Description
To report the number of participants with late radiation morbidity
Late subcutaneous fibrosis and joint stiffness are assessed using the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) late toxicity scoring criteria below:
Subcutaneous tissue: Grade 1(slight fibrosis; subcutaneous fat loss), Grade 2(moderate fibrosis: slight field contracture), Grade 3(severe fibrosis; field contracture >10%), Grade 4(necrosis), Grade 0 (none) Joint stiffness: Grade 1(mild stiffness; slight range of motion loss), Grade 2(Moderate stiffness, pain, range of motion loss), Grade 3(Severe stiffness, pain, range of motion loss), Grade 4(necrosis; complete fixation), Grade 0 (none) Lymphedema is measured according to the criteria of Stern: Score 0(none), Score 1(Mild but definite swelling), Score 2(Moderate), Score 3(Severe, considerable swelling), Grade 4(Very severe (skin shiny & tight)
Time Frame
at 2 years from the start of radiation treatment
Secondary Outcome Measure Information:
Title
Grade 3-5 Adverse Events at 6 Months From the Start of Radiation Treatment.
Description
This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for reporting of adverse events.
Time Frame
6 months
Title
Patterns of Failure at 6 Months From the Start of Radiation Treatment
Description
Prespecified patterns of failure, including local failure, regional failure, distant failure, and death without disease progression at 6 months from the start of radiation treatment measured by CT or MRI scan
Time Frame
6 months
Title
Patterns of Failure at 6 Months
Description
Patterns of failure including local failure, distant failure, distant-disease-free survival, disease-free survival, overall survival rates, and second primary tumor at 6 month from the start of radiation treatment on CT or MRI scan.
Time Frame
6 months
Title
Wound Complication Rates Infection, Dehiscence at 6 Months From the Start of Radiation Treatment.
Description
Wound complications - Major wound complications, such as secondary operations, re-admissions, and/or invasive procedures for wound complication (deep wound packing and/or prolonged dressing changes) due to Infection, dehiscence.
Time Frame
6 months
Title
Report of Late Radiation Morbidity at 2 Years
Description
To report the number of participants with late radiation morbidity using quality of life survey including physical, emotional, social/family and functional well-being.
Time Frame
at 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
98 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven primary soft tissue sarcoma of the upper extremity (including shoulder), lower extremity (including hip) or body trunk (excluding retroperitoneum).
No clinical evidence of distant metastatic disease
Evaluation by surgeon, with documentation that the tumor is resectable
ECOG performance status 0-1
For females of childbearing potential, a serum pregnancy test within 4 weeks prior to registration
Patient must practice adequate contraception
Adequate bone marrow function
Exclusion Criteria:
Patients with sarcoma of the head, neck, intra-abdominal or retroperitoneal region, hand or foot
Histopathology demonstrating rhabdomyosarcoma, extraosseous primitive neuroectodermal tumor (PNET), soft tissue Ewing's sarcoma, osteosarcoma, Kaposi's sarcoma, angiosarcoma, aggressive fibromatosis, dermatofibrosarcoma protuberans or chondrosarcoma
Clinical evidence of regional lymph node or distant metastatic disease
Prior invasive malignancy (except non-melanomatous skin cancer or early stage prostate cancer) unless disease free for a minimum of 3 years
Prior radiotherapy to the potential target anatomic region would result in overlap of radiation fields for current sarcoma
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to used medically acceptable forms of contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Yang, MD
Organizational Affiliation
gyang@llu.edu
Official's Role
Principal Investigator
Facility Information:
Facility Name
Loma Linda University Medical Center / James M. Slater Proton Treatment Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase II Trial of Preoperative Proton Therapy in Soft-tissue Sarcomas of the Extremities and Body Wall
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