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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00589121
First Posted: January 9, 2008
Last Update Posted: July 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

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.


Condition Intervention Phase
Lymphedema Musculoskeletal Complications Radiation Fibrosis Radiation Toxicity Sarcoma Drug: Chemotherapy Radiation: Radiation therapy Procedure: Surgery Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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. ]
    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.

  • 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. ]
    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 [ 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 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.

  • 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. ]
    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 [ 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. ]
    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 [ Time Frame: 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.

  • 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. ]
    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 [ Time Frame: 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 [ Time Frame: From date of surgery to 4 months post-surgery ]
    Estimate rate of patients with acute wound complications with 95% confidence interval assuming binomial distribution.

  • Pattern of First Failure [ Time Frame: 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.

  • Impact of Late Radiation Morbidity (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis, or Joint Stiffness) at 2 Years on the Clinical Measure, Musculoskeletal Tumor Rating Scale (MSTS) [ Time Frame: 2 years after start of treatment (+/- 3 months) ]
  • 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. ]
    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.


Other Outcome Measures:
  • Correlation of Late Radiation Morbidity at 2 Years With the 3 Quality of Life Assessments [Functional Assessment of Cancer Therapy-General (FACTG), Toronto Extremity Salvage Score (TESS), and Sexual Adjustment Questionnaire (SAQ)] [ Time Frame: 2 years after start of treatment (+/- 3 months) ]
  • Comparison of TESS and the MSTS Scores at 2 Years Between Cohort B Patients and the Preoperative Radiotherapy Patients in the NCIC CTG Trial [National Cancer Institute of Canada Clinical Trials Group] [ Time Frame: 2 years after start of treatment (+/- 3 months) ]
  • Comparison of SAQ Scores at 2 Years for Cohort A Patients With Cohort B Patients [ Time Frame: 2 years after start of treatment (+/- 3 months) ]

Enrollment: 98
Study Start Date: March 2008
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A - 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
Drug: Chemotherapy
Up to 6 courses of investigator's choice of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy
Radiation: Radiation therapy
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.
Procedure: 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.
Experimental: Cohort B - No Chemotherapy
Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost
Radiation: Radiation therapy
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.
Procedure: 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.

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00589121


Locations
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Kentucky
Norton Suburban Hospital
Louisville, Kentucky, United States, 40207
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, United States, 48073
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
United States, Pennsylvania
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, Vermont
Norris Cotton Cancer Center - North
Saint Johnsbury, Vermont, United States, 05819
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Canada, Quebec
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: Dian Wang, MD, PhD Medical College of Wisconsin
Study Chair: Scott Okuno, MD Mayo Clinic
Study Chair: Burton L. Eisenberg, MD Norris Cotton Cancer Center
Study Chair: John M. Kane, MD Roswell Park Cancer Institute
Study Chair: David G. Kirsch, MD, PhD Duke Cancer Institute
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00589121     History of Changes
Other Study ID Numbers: RTOG-0630
CDR0000582196
First Submitted: January 5, 2008
First Posted: January 9, 2008
Results First Submitted: August 25, 2016
Results First Posted: July 17, 2017
Last Update Posted: July 17, 2017
Last Verified: June 2017

Keywords provided by Radiation Therapy Oncology Group:
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

Additional relevant MeSH terms:
Fibrosis
Sarcoma
Lymphedema
Radiation Injuries
Radiation Pneumonitis
Pathologic Processes
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Wounds and Injuries
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Lung Injury