LymphedemaPhase 2NCT00589121
Image-Guided Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Shoulder, Arm, Hip, or Leg
A Phase 2 study testing Chemotherapy, Radiation therapy and Surgery in people with Lymphedema and Musculoskeletal Complications, run by Radiation Therapy Oncology Group at 17 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphedema, Musculoskeletal Complications, Radiation Fibrosis
- What is being tested?
- Chemotherapy, Radiation therapy and Surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 17 sitesin 2 countries
- Study dates
- Mar 2008to 21 May 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed primary soft tissue sarcoma of the upper extremity (including shoulder) or lower extremity (including hip)
- Incisional or core biopsy required within the past 8 weeks
- No histopathological diagnosis of any of the following:
- Rhabdomyosarcoma
- Extraosseous primitive neuroectodermal tumor (PNET)
- Soft tissue Ewing sarcoma
- Osteosarcoma
- Kaposi sarcoma
- Angiosarcoma
- Aggressive fibromatosis (desmoid tumor)
- Dermatofibrosarcoma protuberans
- Chondrosarcoma
- Extraskeletal myxoid chondrosarcoma allowed
- Tumor must be surgically resectable, as determined by a surgeon within the past 8 weeks
- Limb-preservation surgery alone would not provide adequate local control, as determined by the surgeon
- No sarcoma of the hand, foot, head, neck, or intra-abdominal or retroperitoneal region or body wall
- No sarcoma ≥ 32 cm in any direction
- No lymph node or distant metastases, according to the following within the past 8 weeks:
- History/physical examination, including a detailed description of the location, size, and stage of the sarcoma
- MRI with contrast of the primary tumor
- The maximum dimension of the primary tumor is measured in MRI images
- CT scan of the chest
- Multiple pulmonary nodules < 8 mm without a histological diagnosis detected incidentally on a non-screening CT scan may be allowed
- CT scan with contrast of the abdomen and pelvis in patients with intermediate- or high-grade sarcoma of the upper thigh
- No recurrent tumor after prior potentially curative therapy
PATIENT CHARACTERISTICS:
- Zubrod performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
- Bilirubin ≤ 1.5 mg/dL*
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 times upper limit of normal*
- Serum creatinine ≤ 1.6 mg/dL OR creatinine clearance ≥ 55 mL/min*
- Left ventricular ejection fraction (LVEF) ≥ 50% by multiple gated acquisition scan (MUGA) or echocardiogram*
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
- No severe, active co-morbidity, including any of the following*:
- Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
- Transmural myocardial infarction within the past 6 months
- Acute bacterial infection or fungal infection requiring intravenous antibiotics
- Acquired Immune Deficiency Syndrome (AIDS) or immunocompromised patients
- HIV testing not required
- No NCI CTCAE v 3.0 grade 3-4 electrolyte abnormalities, including any of the following*:
- Calcium < 7 mg/dL or > 12.5 mg/dL
- Glucose < 40 mg/dL or > 250 mg/dL
- Magnesium < 0.9 mg/dL or > 3 mg/dL
- Potassium < 3mmol/L or > 6 mmol/L
- Sodium < 130 mmol/L or > 155 mmol/L NOTE: *Applies to group 1 only, which was closed to accrual as of 01/08/10)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior excisional biopsy in which the majority of the tumor (≥ 50%) is removed
- No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
- No other concurrent investigational agents
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States14 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
University of Florida Shands Cancer Center
Gainesville, Florida, 32610-0232
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0002
Norton Suburban Hospital
Louisville, Kentucky, 40207
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, 33136
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
CCOP - Christiana Care Health Services
Newark, Delaware, 19713
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, 48073
Norris Cotton Cancer Center - North
Saint Johnsbury, Vermont, 05819
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, 33612-9497
Canada3 sites
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, T6G 1Z2
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, N6A 4L6
McGill Cancer Centre at McGill University
Montreal, Quebec, H2W 1S6
About this study
Official title: A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity
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.
Read the 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.
- Conditions
- Lymphedema, Musculoskeletal Complications, Radiation Fibrosis, Radiation Toxicity, Sarcoma
- Being tested
- Chemotherapy, Radiation therapy, Surgery
- Keywords
- radiation fibrosis, radiation toxicity, lymphedema, musculoskeletal complications, stage I adult soft tissue sarcoma, stage II adult soft tissue sarcoma, adult extraskeletal chondrosarcoma, stage III adult soft tissue sarcoma
- Medical subject headings
- Lymphedema, Radiation Fibrosis Syndrome, Radiation Injuries, Sarcoma, Chondrosarcoma, Extraskeletal Myxoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChemotherapyDrug
Up to 6 courses of investigator's choice of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy
Radiation therapyRadiation
Preoperative IGRT (3D-CRT or IMRT): If receiving neoadjuvant or adjuvant chemotherapy or no chemotherapy: 50 Gy (2 Gy once a day, 5 times a week). If receiving concurrent or interdigitated chemotherapy: 44 Gy (2 Gy once a day, 5 times a week). Postoperative radiotherapy boost for patients with positive margins following surgery: 16 Gy (2 Gy once a day, 5 times a week) external beam radiation therapy or 16 Gy at ≤ 80 cGy per hour brachytherapy or 3.4 Gy/fraction in 4 fractions brachytherapy or 10-12.5 Gy in a single fraction intraoperative radiation therapy boost.
SurgeryProcedure or surgery
Resection of the sarcoma with the goal of having negative pathologic margins. Every effort should be made to have limb preservation surgery unless there is documented evidence of tumor progression that would require amputation for an appropriate negative margin resection. All lesions of the extremities should be treated with wide excision.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A - Chemotherapy | Experimental | Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost Receives: Drug: Chemotherapy; Radiation: Radiation therapy; Procedure: Surgery |
| Cohort B - No Chemotherapy | Experimental | Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost Receives: Radiation: Radiation therapy; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: 2 years after start of treatment (+/- 3 months)
Secondary outcomes (12)
Local Failure Rate at Two Years
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.
Measured: From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Regional Failure Rate at Two Years
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.
Measured: From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Distant Failure Rate at Two Years
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.
Measured: 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 Rate at Two Years
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.
Measured: From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.
Disease-free Survival Rate at Two Years
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.
Measured: 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.
Overall Survival Rate at Two Years
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.
Measured: From registration to date of death or last follow-up. Report at time of primary outcome measure analysis.
Second Primary Tumor Rate at Two Years
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.
Measured: From registration to date of failure (second primary tumor) or death or last follow-up. Report at time of primary outcome measure analysis.
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
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.
Measured: 2 years after start of treatment (+/- 3 months)
Percentage of Patients With Wound Complications
Estimate rate of patients with acute wound complications with 95% confidence interval assuming binomial distribution.
Measured: From date of surgery to 4 months post-surgery
Pattern of First Failure
Pattern of first failure including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression.
Measured: From registration to date of local, regional or distant progression. Report at time of primary outcome measure analysis.
Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two 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.
Measured: From start of treatment to 2 years.
Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events
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.
Measured: From start of treatment to last follow-up. Analysis can occur at or after time of primary outcome measure analysis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2008 (estimated)
- Study startMar 2008
- Primary completionDec 2012
- Study completion21 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LymphedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radiation Therapy Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), NRG Oncology
- Responsible party
- Sponsor
- Investigators
- Dian Wang, MD, PhD, Principal investigator, Medical College of WisconsinScott Okuno, MD, Study chair, Mayo ClinicBurton L. Eisenberg, MD, Study chair, Norris Cotton Cancer CenterJohn M. Kane, MD, Study chair, Roswell Park Cancer InstituteDavid G. Kirsch, MD, PhD, Study chair, Duke Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00589121
- Sponsor's protocol ID
- RTOG-0630
- Other IDs
- CDR0000582196
- Status last verified
- Jun 2018
- First submitted
- 5 Jan 2008
- Last updated
- 12 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Wang D, Harris J, Kraybill WG, Eisenberg B, Kirsch DG, Ettinger DS, Kane JM 3rd, Barry PN, Naghavi A, Freeman CR, Chen YL, Hitchcock YJ, Bedi M, Salerno KE, Severin D, Godette KD, Larrier NA, Curran WJ Jr, Torres-Saavedra PA, Lucas DR. Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials. JAMA Oncol. 2023 May 1;9(5):646-655. doi: 10.1001/jamaoncol.2023.0042.
PubMed 36995690Wang D, Zhang Q, Eisenberg BL, Kane JM, Li XA, Lucas D, Petersen IA, DeLaney TF, Freeman CR, Finkelstein SE, Hitchcock YJ, Bedi M, Singh AK, Dundas G, Kirsch DG. Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial. J Clin Oncol. 2015 Jul 10;33(20):2231-8. doi: 10.1200/JCO.2014.58.5828. Epub 2015 Feb 9.
PubMed 25667281
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity
- ClinicalTrials.gov ID
- NCT00589121
- Acronym / sponsor ID
- RTOG-0630
- Conditions
- Lymphedema, Musculoskeletal Complications, Radiation Fibrosis, Radiation Toxicity, Sarcoma
- Keywords
- radiation fibrosis, radiation toxicity, lymphedema, musculoskeletal complications, stage I adult soft tissue sarcoma, stage II adult soft tissue sarcoma, adult extraskeletal chondrosarcoma, stage III adult soft tissue sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Radiation Therapy Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI), NRG Oncology
- Study start
- Mar 2008 (actual)
- Primary completion
- Dec 2012 (actual)
- Study completion
- 21 May 2018 (actual)
- First posted
- 9 Jan 2008 (estimated)
- Results
- Posted 17 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A - Chemotherapy | Experimental | Drug: Chemotherapy, Radiation: Radiation therapy, Procedure: SurgeryRadiation 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 | Experimental | Radiation: Radiation therapy, Procedure: SurgeryRadiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChemotherapyUp to 6 courses of investigator's choice of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy | Drug | Cohort A - Chemotherapy |
| Radiation therapyPreoperative IGRT (3D-CRT or IMRT): If receiving neoadjuvant or adjuvant chemotherapy or no chemotherapy: 50 Gy (2 Gy once a day, 5 times a week). If receiving concurrent or interdigitated chemotherapy: 44 Gy (2 Gy once a day, 5 times a week). Postoperative radiotherapy boost for patients with positive margins following surgery: 16 Gy (2 Gy once a day, 5 times a week) external beam radiation therapy or 16 Gy at ≤ 80 cGy per hour brachytherapy or 3.4 Gy/fraction in 4 fractions brachytherapy or 10-12.5 Gy in a single fraction intraoperative radiation therapy boost. | Radiation | Cohort A - Chemotherapy, Cohort B - No Chemotherapy |
| SurgeryResection of the sarcoma with the goal of having negative pathologic margins. Every effort should be made to have limb preservation surgery unless there is documented evidence of tumor progression that would require amputation for an appropriate negative margin resection. All lesions of the extremities should be treated with wide excision. | Procedure or surgery | Cohort A - Chemotherapy, Cohort B - No Chemotherapy |
Primary outcome
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
Time frame: 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.
12 secondary outcomes
Local Failure Rate at Two Years
Time frame: From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Regional Failure Rate at Two Years
Time frame: From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Distant Failure Rate at Two Years
Time frame: 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 Rate at Two Years
Time frame: From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.
Disease-free Survival Rate at Two Years
Time frame: 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.
Overall Survival Rate at Two Years
Time frame: From registration to date of death or last follow-up. Report at time of primary outcome measure analysis.
Second Primary Tumor Rate at Two Years
Time frame: From registration to date of failure (second primary tumor) or death or last follow-up. Report at time of primary outcome measure analysis.
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
Time frame: 2 years after start of treatment (+/- 3 months)
Percentage of Patients With Wound Complications
Time frame: From date of surgery to 4 months post-surgery
Pattern of First Failure
Time frame: From registration to date of local, regional or distant progression. Report at time of primary outcome measure analysis.
Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years
Time frame: From start of treatment to 2 years.
Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events
Time frame: From start of treatment to last follow-up. Analysis can occur at or after time of primary outcome measure analysis.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36995690Wang D, Harris J, Kraybill WG, Eisenberg B, Kirsch DG, Ettinger DS, Kane JM 3rd, Barry PN, Naghavi A, Freeman CR, Chen YL, Hitchcock YJ, Bedi M, Salerno KE, Severin D, Godette KD, Larrier NA, Curran WJ Jr, Torres-Saavedra PA, Lucas DR. Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials. JAMA Oncol. 2023 May 1;9(5):646-655. doi: 10.1001/jamaoncol.2023.0042.
- Derived from this study: PubMed 25667281Wang D, Zhang Q, Eisenberg BL, Kane JM, Li XA, Lucas D, Petersen IA, DeLaney TF, Freeman CR, Finkelstein SE, Hitchcock YJ, Bedi M, Singh AK, Dundas G, Kirsch DG. Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial. J Clin Oncol. 2015 Jul 10;33(20):2231-8. doi: 10.1200/JCO.2014.58.5828. Epub 2015 Feb 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dian Wang, MD, PhD principal investigator
Medical College of Wisconsin
Scott Okuno, MD study chair
Mayo Clinic
Burton L. Eisenberg, MD study chair
Norris Cotton Cancer Center
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chemotherapy, Radiation therapy and Surgery in people with Lymphedema and Musculoskeletal Complications, run by Radiation Therapy Oncology Group at 17 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 2 years after start of treatment (+/- 3 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00589121, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2019; AzTrials last refreshed its copy on 6 Nov 2026.