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

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00589121
• Other study ID #: RTOG-0630
• Secondary ID: CDR0000582196
• Status: Completed
• Phase: Phase 2
• Start date: March 2008
• Est. completion date: May 21, 2018

Study information

• Verified date: June 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: May 21, 2018
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Norton Suburban Hospital	Louisville	Kentucky
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)]		2 years after start of treatment (+/- 3 months)
Other	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]		2 years after start of treatment (+/- 3 months)
Other	Comparison of SAQ Scores at 2 Years for Cohort A Patients With Cohort B Patients		2 years after start of treatment (+/- 3 months)
Primary	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	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.	2 years after start of treatment (+/- 3 months)
Secondary	Local Failure Rate at Two Years	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.	From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Secondary	Regional Failure Rate at Two Years	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.	From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Secondary	Distant Failure Rate at Two Years	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.	From registration to date of failure (distant progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Secondary	Distant Disease-free Survival Rate at Two Years	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.	From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.
Secondary	Disease-free Survival Rate at Two Years	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.	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.
Secondary	Overall Survival Rate at Two Years	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.	From registration to date of death or last follow-up. Report at time of primary outcome measure analysis.
Secondary	Second Primary Tumor Rate at Two Years	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.	From registration to date of failure (second primary tumor) or death or last follow-up. Report at time of primary outcome measure analysis.
Secondary	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	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.	2 years after start of treatment (+/- 3 months)
Secondary	Percentage of Patients With Wound Complications	Estimate rate of patients with acute wound complications with 95% confidence interval assuming binomial distribution.	From date of surgery to 4 months post-surgery
Secondary	Pattern of First Failure	Pattern of first failure including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression.	From registration to date of local, regional or distant progression. Report at time of primary outcome measure analysis.
Secondary	Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years	The Musculoskeletal Tumor Rating Scale (MSTS) is a measure of physical function across 7 items, completed by the physician (preferably by the Orthopedic Surgeon or Surgical Oncologist) or the physician's designated staff. The 7 items are: pain, range of motion, strength, joint stability, joint deformity, emotional, acceptance, and overall function. Each item is scored from 0-5 (worst possible to best possible condition). The item scores are summed to get the total score which ranges from 0-35.; Late radiation morbidity is defined as = grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness. 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.	From start of treatment to 2 years.
Secondary	Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events	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.	From start of treatment to last follow-up. Analysis can occur at or after time of primary outcome measure analysis.