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

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00589121

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: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy	Phase II

Study Type:	Interventional
Study Design:	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:

Genetics Home Reference related topics: lymphedema-distichiasis syndrome

MedlinePlus related topics: Cancer Lymphedema Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis or joint stiffness) at 2 years from the start of radiotherapy as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
Other grade 3-5 adverse events as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
Pattern of first failure [ Designated as safety issue: No ]
Time to local failure [ Designated as safety issue: No ]
Time to regional failure [ Designated as safety issue: No ]
Time to distant failure [ Designated as safety issue: No ]
Distant disease-free survival [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Time to second primary tumor [ Designated as safety issue: No ]
Wound complications [ Designated as safety issue: No ]
Impact of late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years on the clinical measure, Musculoskeletal Tumor Rating Scale (MTRS) [ Designated as safety issue: Yes ]

Estimated Enrollment:	83
Study Start Date:	March 2008
Estimated Primary Completion Date:	November 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: chemotherapy Up to 6 courses of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy Radiation: 3-dimensional conformal radiation therapy Performed preoperatively once daily, 5 days a week, for 4½-5 weeks Radiation: intensity-modulated radiation therapy Performed preoperatively once daily, 5 days a week, for 4½-5 weeks
Experimental: Group 2 Patients undergo 3D-CRT or IMRT once daily, 5 days a week, for 5 weeks.	Radiation: 3-dimensional conformal radiation therapy Performed preoperatively once daily, 5 days a week, for 4½-5 weeks Radiation: intensity-modulated radiation therapy Performed preoperatively once daily, 5 days a week, for 4½-5 weeks

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 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 (MTRS).

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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*
AST or ALT ≤ 2 times upper limit of normal*
Serum creatinine ≤ 1.6 mg/dL OR creatinine clearance ≥ 55 mL/min*
LVEF ≥ 50% by 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

Please refer to this study by its ClinicalTrials.gov identifier: 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)

Investigators

Study Chair:	Dian Wang, MD, PhD	Medical College of Wisconsin
Investigator:	Scott Okuno, MD	Mayo Clinic
Investigator:	Burton L. Eisenberg, MD	Norris Cotton Cancer Center
Investigator:	John M. Kane, MD	Roswell Park Cancer Institute
Investigator:	David G. Kirsch, MD, PhD	Duke Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Walter John Curran, Jr, Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00589121 History of Changes
Other Study ID Numbers:	CDR0000582196, RTOG-0630
Study First Received:	January 5, 2008
Last Updated:	December 13, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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
Lymphedema
Radiation Injuries
Sarcoma
Radiation Pneumonitis
Pathologic Processes
Lymphatic Diseases
Wounds and Injuries

Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Lung Injury

ClinicalTrials.gov processed this record on February 09, 2012