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:
Collaborators:
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00589121
First received: January 5, 2008
Last updated: July 21, 2014
Last verified: July 2014
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: 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:
  • 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: From start of treatment to 2 years ] [ Designated as safety issue: Yes ]
    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


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 [ Time Frame: From start of treatment to 2 years ] [ Designated as safety issue: Yes ]
  • Other grade 3-5 adverse events as measured by CTCAE v3.0 [ Time Frame: From start of treatment to last follow-up ] [ Designated as safety issue: Yes ]
  • Pattern of first failure [ Time Frame: From registration to date of local, regional or distant progression ] [ Designated as safety issue: No ]
  • Time to local failure [ Time Frame: From registration to date of failure (local progression) or death or last follow-up ] [ Designated as safety issue: No ]
  • Time to regional failure [ Time Frame: From registration to date of failure (regional progression) or death or last follow-up ] [ Designated as safety issue: No ]
  • Time to distant failure [ Time Frame: From registration to date of failure (distant progression) or death or last follow-up ] [ Designated as safety issue: No ]
  • Distant disease-free survival [ Time Frame: From registration to date of failure (distant progression or death) or last follow-up ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: From registration to date of failure (local, regional or distant progression or death) or last follow-up ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From registration to date of death or last follow-up ] [ Designated as safety issue: No ]
  • Time to second primary tumor [ Time Frame: From registration to date of failure (second primary tumor) or death or last follow-up ] [ Designated as safety issue: No ]
  • Wound complications [ Time Frame: From date of surgery to 4 months post-surgery ] [ Designated as safety issue: Yes ]
  • 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) [ Time Frame: From start of treatment to 2 years ] [ 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 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.

  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*
  • 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
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, see Learn About Clinical Studies.

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
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

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00589121     History of Changes
Other Study ID Numbers: RTOG-0630, CDR0000582196
Study First Received: January 5, 2008
Last Updated: July 21, 2014
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on October 19, 2014