Image-Guided Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Shoulder, Arm, Hip, or Leg

Phase 2

Completed

• Conditions: Lymphedema; Musculoskeletal Complications; Radiation Fibrosis; Radiation Toxicity; Sarcoma
• Interventions: Drug: Chemotherapy; Radiation: Radiation therapy; Procedure: Surgery

• Registration Number: NCT00589121
• Lead Sponsor: Radiation Therapy Oncology Group

Brief Summary

RATIONALE: Image-guided radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a lower dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This phase II trial is studying the side effects and how well image-guided radiation therapy works in treating patients with primary soft tissue sarcoma of the shoulder, arm, hip, or leg.

Detailed Description

OBJECTIVES:

Primary

* To determine the effect of reduced radiation volume using image-guided radiotherapy (IGRT) on lymphedema ≥ grade 2, subcutaneous fibrosis, and joint stiffness at 2 years in patients with primary soft tissue sarcoma of the extremity.

Secondary

* To estimate the rates of other grade 3-5 adverse events as measured by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0.

* To determine the pattern of first failure, including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression.

* To estimate the rates of local failure, local-regional failure, distant failure, distant disease-free survival, disease-free survival, overall survival, and second primary tumor.

* To estimate the rate of wound complications.

* To correlate the degree of late radiation morbidity (defined as any lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years with scores on the clinical measure, Musculoskeletal Tumor Rating Scale (MSTS).

OUTLINE: This is a multicenter study.

* Neoadjuvant radiotherapy: Patients are assigned to 1 of 2 treatment groups (group 1 closed to accrual as of 01/08/10).

* Group 1 (closed to accrual as of 01/08/10): Patients undergo 3-D conformal radiotherapy (3D-CRT) or intensity-modulated therapy (IMRT) once daily, 5 days a week, for 4½-5 weeks. Patients also receive up to 6 courses of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy.

* Group 2: Patients undergo 3D-CRT or IMRT once daily, 5 days a week, for 5 weeks.

* Surgery: At 4-8 weeks after completion of neoadjuvant radiotherapy, patients undergo surgical resection of the tumor. Patients with positive tumor margins (residual tumor) undergo intraoperative radiotherapy boost or proceed to adjuvant radiotherapy within 2 weeks after surgery.

* Adjuvant radiotherapy: Patients undergo either external-beam radiotherapy (EBRT) once daily for 8 fractions or brachytherapy.

After completion of study treatment, patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Timeline

• Study First Submitted: 2008-01-05
• Study First Submitted QC: 2008-01-05
• Study First Posted: 2008-01-09
• Study Start: 2008-03
• Primary Completion: 2012-12
• Results First Submitted: 2016-08-25
• Results First Submitted QC: 2017-06-19
• Results First Posted: 2017-07-17
• Study Completion: 2018-05-21
• Status Verified: 2018-06
• Last Update Submitted: 2019-06-03
• Last Update Posted: 2019-06-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A - Chemotherapy	Chemotherapy	Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost
Cohort A - Chemotherapy	Radiation therapy	Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost
Cohort A - Chemotherapy	Surgery	Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost
Cohort B - No Chemotherapy	Radiation therapy	Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost
Cohort B - No Chemotherapy	Surgery	Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost

Primary Outcome Measures

Name	Time	Method
Rate of Late Radiation Morbidity (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis, or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by EORTC/RTOG Criteria	2 years after start of treatment (+/- 3 months)	The rate of patients with late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years from the start of radiotherapy as measured by EORTC(European Organisation for Research and Treatment of Cancer)/RTOG (Radiation Therapy Oncology Group) criteria. Grade refers to the severity of the morbidity. The RTOG/EORTC Late Radiation Morbidity Scoring Schema assigns Grades 1 through 5 with unique clinical descriptions of severity for each morbidity based on this general guideline: Grade 1 Mild , Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to morbidity.

Secondary Outcome Measures

Name	Time	Method
Pattern of First Failure	From registration to date of local, regional or distant progression. Report at time of primary outcome measure analysis.	Pattern of first failure including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression.
Distant Disease-free Survival Rate at Two Years	From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.	Distant disease-free survival is defined as the time from registration to date of failure (distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method.
Disease-free Survival Rate at Two Years	From registration to date of failure (local, regional or distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.	Disease-free survival is defined as the time from registration to date of failure (local, regional, or distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method.
Overall Survival Rate at Two Years	From registration to date of death or last follow-up. Report at time of primary outcome measure analysis.	Overall survival is defined as the time from registration to date of death or last follow-up. Two year survival rate and 95% confidence interval were estimated by the Kaplan-Meier method.
Local Failure Rate at Two Years	From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis.	Local failure is defined as the time from registration to date of failure (local progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Second Primary Tumor Rate at Two Years	From registration to date of failure (second primary tumor) or death or last follow-up. Report at time of primary outcome measure analysis.	Second primary tumor is defined as the time from registration to date of failure (second primary tumor) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Late Radiation Morbidity Rate (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by CTCAE v3.0	2 years after start of treatment (+/- 3 months)	Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Percentage of Patients With Wound Complications	From date of surgery to 4 months post-surgery	Estimate rate of patients with acute wound complications with 95% confidence interval assuming binomial distribution.
Regional Failure Rate at Two Years	From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis.	Regional failure is defined as the time from registration to date of failure (regional progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Distant Failure Rate at Two Years	From registration to date of failure (distant progression) or death or last follow-up. Report at time of primary outcome measure analysis.	Distant failure is defined as the time from registration to date of failure (distant progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years	From start of treatment to 2 years.	The Musculoskeletal Tumor Rating Scale (MSTS) is a measure of physical function across 7 items, completed by the physician (preferably by the Orthopedic Surgeon or Surgical Oncologist) or the physician's designated staff. The 7 items are: pain, range of motion, strength, joint stability, joint deformity, emotional, acceptance, and overall function. Each item is scored from 0-5 (worst possible to best possible condition). The item scores are summed to get the total score which ranges from 0-35.; Late radiation morbidity is defined as ≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events	From start of treatment to last follow-up. Analysis can occur at or after time of primary outcome measure analysis.	Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Trial Locations

Locations (17)

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

Mayo Clinic - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

CCOP - Christiana Care Health Services; 🇺🇸 Newark, Delaware, United States

University of Florida Shands Cancer Center; 🇺🇸 Gainesville, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center - Miami; 🇺🇸 Miami, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida; 🇺🇸 Tampa, Florida, United States

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Norris Cotton Cancer Center - North; 🇺🇸 Saint Johnsbury, Vermont, United States

William Beaumont Hospital - Royal Oak Campus; 🇺🇸 Royal Oak, Michigan, United States

Norton Suburban Hospital; 🇺🇸 Louisville, Kentucky, United States

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Medical College of Wisconsin Cancer Center; 🇺🇸 Milwaukee, Wisconsin, United States

Cross Cancer Institute at University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

London Regional Cancer Program at London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

McGill Cancer Centre at McGill University; 🇨🇦 Montreal, Quebec, Canada

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States