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A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity

Phase 2
18 Years
Open (Enrolling)
Lymphedema, Musculoskeletal Complications, Radiation Fibrosis, Radiation Toxicity, Sarcoma

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Trial Information

A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity



- 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.


- 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 (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.

Inclusion Criteria


- 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

- 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

- 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


- 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

- 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)


- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

Late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years from the start of radiotherapy as measured by European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria

Outcome Time Frame:

From start of treatment to 2 years

Safety Issue:


Principal Investigator

Dian Wang, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Medical College of Wisconsin


United States: Federal Government

Study ID:




Start Date:

March 2008

Completion Date:

Related Keywords:

  • Lymphedema
  • Musculoskeletal Complications
  • Radiation Fibrosis
  • Radiation Toxicity
  • Sarcoma
  • 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
  • Fibrosis
  • Lymphedema
  • Radiation Injuries
  • Sarcoma
  • Radiation Pneumonitis



Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic - Jacksonville Jacksonville, Florida  32224
Mayo Clinic Cancer Center Rochester, Minnesota  55905
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire  03756-0002
University of Florida Shands Cancer Center Gainesville, Florida  32610-0232
William Beaumont Hospital - Royal Oak Campus Royal Oak, Michigan  48073
Massachusetts General Hospital Boston, Massachusetts  02114-2617
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida Tampa, Florida  33612
University of Miami Sylvester Comprehensive Cancer Center - Miami Miami, Florida  33136
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center Hershey, Pennsylvania  17033-0850
Norris Cotton Cancer Center - North Saint Johnsbury, Vermont  05819
Norton Suburban Hospital Louisville, Kentucky  40207