Skip to main content
Back to Trials
NCT07615049PHASE3Recruiting

Testing Short-Course Radiation Versus Standard-Course Radiation for Soft Tissue Sarcomas That Need Surgery and Radiation

SWOG Cancer Research Network

Start Date

12/2/2026

Completion Date

4/30/2030

Summary

This clinical trial compares the effect of short-course ultrahypofractionated radiation therapy over 5 days (UHRT-5) to standard-course radiation therapy over 25 days (RT-25) in treating patients with soft tissue sarcomas of the extremities that may be primary or that may have come back to nearby tissue or lymph nodes after a period of improvement (locally recurrent) and that can be removed by surgery (resectable). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. 3-dimensional (3D) conformal radiation therapy (CRT) uses a computer to create a 3D picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. Intensity-modulated radiation therapy (IMRT) is a type of 3D radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Standard-course (fractionated) radiation divides the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. Ultrahypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving UHRT-5 may be as effective as RT-25 in treating patients with primary or locally recurrent soft tissue sarcomas of the extremities that are resectable. It may also improve quality of life by requiring fewer treatments.

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate whether the incidence of local tumor recurrence at 2-years after randomization with short-course radiation is non-inferior to standard-course radiation among participants with high-risk, resectable soft tissue sarcoma. SECONDARY OBJECTIVES: I. To estimate and compare between arms the incidence of acute wound complications. II. To estimate and compare between arms the incidence of late-term complications associated with radiation at 2-years post-surgery. III. To estimate and compare between arms changes in physician-assessed functional outcome from pre-randomization to 12 and 24 months post surgery using the Musculoskeletal Tumor Society Scoring system. IV. To estimate and compare between arms overall survival, progression-free survival, and distant-metastasis-free survival measured from randomization. EXPLORATORY OBJECTIVES: I. To estimate and compare between arms the incidence of local tumor recurrence at 2 years using a per-protocol analysis. II. To estimate and compare between arms the incidence of delayed wound healing. III. To report the type of surgical resection by treatment arm, including limb-salvage versus amputation and margin status (R0, R1, or R2). IV. To describe the use of supportive therapy medications given with radiation therapy separately by treatment arm. V. To describe the use of adjuvant therapy post-surgery separately by treatment arm. BANKING OBJECTIVE: I. To bank tissue specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients undergo RT-25 with 3D CRT or IMRT once daily (QD) for up to 5 fractions per week for 25 fractions over a minimum of 32 calendar days and maximum of 49 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo magnetic resonance imaging (MRI), computed tomography (CT), and blood sample collection throughout the study. ARM 2: Patients undergo UHRT-5 with 3D CRT or IMRT QD for up to 5 fractions per week for 5 fractions over a minimum of 5 calendar days and maximum of 14 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo MRI, CT, and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 4 months, every 6 months after surgery for up to 5 years, and then annually for up to 10 years after randomization.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Participants must have histological evidence of a soft tissue sarcoma from core or incisional biopsy. Participants must have a primary or locally recurrent tumor. Stage II-IIIB (by American Joint Committee on Cancer \[AJCC\] 8th edition) soft tissue sarcoma is required * Prior partial excision or partial excisional biopsy of the tumor, with imaging evidence of gross residual disease \> 1cm in longest dimension (stage II-IIIB) * Participants must have a primary site of disease in the extremity, including the shoulder girdle and hip girdle but excluding the hands and feet * Participants with primary sites of trunk, head, neck, or intra-abdominal, intrapelvic, or retroperitoneal region are not eligible * Participants with extension of the primary tumor into adjacent regions (e.g. torso, hands, feet) are eligible * Participants must have an MRI of the primary site within 90 days prior to randomization. The MRI field of view must contain the entirety of the tumor (may be accomplished with multiple MRI scans). MRI must contain axial acquired T1 weighted with fat suppression, T1 weighted sequence with gadolinium contrast with fat suppression, and T2 weighted fat suppression sequence * Participants must have no evidence of metastatic disease by CT imaging of the chest (or positron emission tomography \[PET\] CT), within 28 days before randomization * Given the lack of specificity of chest CT, pulmonary nodule(s) ≤ 5 mm without a histological diagnosis are not exclusionary * Participants with pulmonary nodule(s) measuring 6-10 mm on chest CT are eligible if the nodules appear stable compared to prior chest imaging from at least 6 months ago, or if an fludeoxyglucose F-18 (18FDG)-PET scan indicates that the nodules are unlikely to be metastatic disease * Pulmonary nodules \> 10 mm should be considered metastatic unless proven otherwise by biopsy/resection or stable appearance for at least 6 months on imaging * Participants must not have fungating tumor. (i.e., tumor breakthrough of skin) * Participants must not have myxoid liposarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, gastrointestinal stromal tumor, osteosarcoma, neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, desmoplastic small round cell tumor, Ewing sarcoma, or sarcoma arising from bone * Participants must not have known brain metastases. Brain imaging studies are not required for eligibility if the participant has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease * Participants must have been evaluated by a surgeon, and it must have been determined that they are a good candidate for a limb salvage resection with an expectation of negative margins, within 35 days prior to randomization. Anticipated positive margins on fixed critical structures are allowed * Participants must not have had prior treatment for the current tumor (systemic therapy, radiation, or complete surgical resection) * Participants must not have had prior radiation to the anatomical site * Participants must be ≥ 18 years old at the time of randomization * Participants must have Zubrod performance status of 0-2 * Participants must have medical history and physical exam within 28 days prior to randomization. History and physical examination must include a description of the location of the tumor, including lateralization and extremity * Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen * Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen * Participants must not have uncontrolled intercurrent illnesses or any other significant condition(s) that would make this protocol unreasonably hazardous * Participants with a history human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration * Participants registered by sites located in the United States only must be offered the opportunity to participate in specimen banking * NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines * For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

Interventions

RADIATION

3-Dimensional Conformal Radiation Therapy

RADIATION

3-Dimensional Conformal Radiation Therapy

PROCEDURE

Biospecimen Collection

PROCEDURE

Computed Tomography

RADIATION

Intensity-Modulated Radiation Therapy

RADIATION

Intensity-Modulated Radiation Therapy

PROCEDURE

Magnetic Resonance Imaging

PROCEDURE

Surgical Procedure

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Recurrent Soft Tissue Sarcoma of the Trunk and ExtremitiesResectable Soft Tissue Sarcoma of the Trunk and ExtremitiesSoft Tissue Sarcoma of the Trunk and ExtremitiesStage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8

Locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama 35233

United States

Kaiser Permanente-Anaheim

Anaheim, California 92806

United States

Kaiser Permanente-Deer Valley Medical Center

Antioch, California 94531

United States

Kaiser Permanente-Bellflower

Bellflower, California 90706

United States

Kaiser Permanente Dublin

Dublin, California 94568

United States

Kaiser Permanente-Fremont

Fremont, California 94538

United States

Fresno Cancer Center

Fresno, California 93720

United States

Kaiser Permanente Fresno Orchard Plaza

Fresno, California 93720

United States

Kaiser Permanente-Fresno

Fresno, California 93720

United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California 92612

United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California 90027

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Kaiser Permanente- Modesto MOB II

Modesto, California 95356

United States

Kaiser Permanente Oakland-Broadway

Oakland, California 94611

United States

Kaiser Permanente-Oakland

Oakland, California 94611

United States

Kaiser Permanente-Ontario

Ontario, California 91761

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California 92868

United States

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California 95670

United States

Kaiser Permanente- Marshall Medical Offices

Redwood City, California 94063

United States

Kaiser Permanente-Richmond

Richmond, California 94801

United States

Rohnert Park Cancer Center

Rohnert Park, California 94928

United States

Kaiser Permanente-Roseville

Roseville, California 95661

United States

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California 95678

United States

Kaiser Permanente Downtown Commons

Sacramento, California 95814

United States

Kaiser Permanente-South Sacramento

Sacramento, California 95823

United States

South Sacramento Cancer Center

Sacramento, California 95823

United States

Kaiser Permanente-San Francisco

San Francisco, California 94115

United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California 95119

United States

Kaiser Permanente San Leandro

San Leandro, California 94577

United States

Kaiser San Rafael-Gallinas

San Rafael, California 94903

United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California 95051

United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California 95403

United States

Kaiser Permanente Cancer Treatment Center

South San Francisco, California 94080

United States

Kaiser Permanente-South San Francisco

South San Francisco, California 94080

United States

Kaiser Permanente-Stockton

Stockton, California 95210

United States

Kaiser Permanente Medical Center-Vacaville

Vacaville, California 95688

United States

Kaiser Permanente-Vallejo

Vallejo, California 94589

United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California 94596

United States

Helen F Graham Cancer Center

Newark, Delaware 19713

United States

Medical Oncology Hematology Consultants PA

Newark, Delaware 19713

United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware 19718

United States

Grady Health System

Atlanta, Georgia 30303

United States

Emory University Hospital Midtown

Atlanta, Georgia 30308

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia 30342

United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois 62526

United States

Decatur Memorial Hospital

Decatur, Illinois 62526

United States

Billings Clinic Cancer Center

Billings, Montana 59101

United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire 03756

United States

Dartmouth Cancer Center - Manchester/ DCC Manchester

Manchester, New Hampshire 03104

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Montefiore Medical Center-Einstein Campus

The Bronx, New York 10461

United States

Montefiore Medical Center-Weiler Hospital

The Bronx, New York 10461

United States

Montefiore Medical Center - Moses Campus

The Bronx, New York 10467

United States

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania 19317

United States

Geisinger Medical Oncology-Lewisburg

Lewisburg, Pennsylvania 17837

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania 18711

United States

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont 05819

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia 23298

United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin 54449

United States

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin 53051

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Froedtert and MCW Moorland Reserve Health Center

New Berlin, Wisconsin 53151

United States

Drexel Town Square Health Center

Oak Creek, Wisconsin 53154

United States

Froedtert West Bend Hospital/Kraemer Cancer Center

West Bend, Wisconsin 53095

United States

Marshfield Medical Center - Weston

Weston, Wisconsin 54476

United States