Clinical trial NCT00589121: Image-Guided Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Shoulder, Arm, Hip, or Leg
Official title: A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2008-01-09
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
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
timeFrame: 2 years after start of treatment (+/- 3 months)
Secondary outcomes:
measure: Local Failure Rate at Two Years
timeFrame: From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis.
measure: Regional Failure Rate at Two Years
timeFrame: From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis.
measure: Distant Failure Rate at Two Years
timeFrame: From registration to date of failure (distant progression) or death or last follow-up. Report at time of primary outcome measure analysis.
measure: Distant Disease-free Survival Rate at Two Years
timeFrame: From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.
measure: Disease-free Survival Rate at Two Years
timeFrame: 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.
measure: Overall Survival Rate at Two Years
timeFrame: From registration to date of death or last follow-up. Report at time of primary outcome measure analysis.
measure: Second Primary Tumor Rate at Two Years
timeFrame: From registration to date of failure (second primary tumor) or death or last follow-up. Report at time of primary outcome measure analysis.
measure: 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
timeFrame: 2 years after start of treatment (+/- 3 months)
measure: Percentage of Patients With Wound Complications
timeFrame: From date of surgery to 4 months post-surgery
measure: Pattern of First Failure
timeFrame: From registration to date of local, regional or distant progression. Report at time of primary outcome measure analysis.
measure: Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years
timeFrame: From start of treatment to 2 years.
measure: Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events
timeFrame: From start of treatment to last follow-up. Analysis can occur at or after time of primary outcome measure analysis.
Other outcomes:
measure: 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)]
timeFrame: 2 years after start of treatment (+/- 3 months)
measure: 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]
timeFrame: 2 years after start of treatment (+/- 3 months)
measure: Comparison of SAQ Scores at 2 Years for Cohort A Patients With Cohort B Patients
timeFrame: 2 years after start of treatment (+/- 3 months)
Locations:
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Louisville
country: United States
facility: Norton Suburban Hospital
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center - North
state: Vermont
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: Medical College of Wisconsin
name: Dian Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Scott Okuno, MD
role: STUDY_CHAIR
affiliation: Norris Cotton Cancer Center
name: Burton L. Eisenberg, MD
role: STUDY_CHAIR
affiliation: Roswell Park Cancer Institute
name: John M. Kane, MD
role: STUDY_CHAIR
affiliation: Duke Cancer Institute
name: David G. Kirsch, MD, PhD
role: STUDY_CHAIR
References:
citation: Wang 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.