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

NCT ID: NCT00589121

Last Updated: 2019-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2018-05-21

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.

Conditions

Lymphedema; Musculoskeletal Complications; Radiation Fibrosis; Radiation Toxicity; Sarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A - Chemotherapy

Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

Up to 6 courses of investigator's choice of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy

Radiation therapy

Intervention Type: RADIATION

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.

Surgery

Intervention Type: PROCEDURE

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.

Cohort B - No Chemotherapy

Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

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.

Surgery

Intervention Type: PROCEDURE

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.

Interventions

Chemotherapy

Up to 6 courses of investigator's choice of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy

Intervention Type: DRUG

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.

Intervention Type: RADIATION

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dian Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Scott Okuno, MD

Role: STUDY_CHAIR

Mayo Clinic

Burton L. Eisenberg, MD

Role: STUDY_CHAIR

Norris Cotton Cancer Center

John M. Kane, MD

Role: STUDY_CHAIR

Roswell Park Cancer Institute

David G. Kirsch, MD, PhD

Role: STUDY_CHAIR

Duke Cancer Institute

Locations

CCOP - Christiana Care Health Services

Newark, Delaware, United States

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Norton Suburban Hospital

Louisville, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Norris Cotton Cancer Center - North

Saint Johnsbury, Vermont, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

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, Canada

Countries

United States; Canada

References

Wang D, Harris J, Kraybill WG, Eisenberg B, Kirsch DG, Ettinger DS, Kane JM 3rd, Barry PN, Naghavi A, Freeman CR, Chen YL, Hitchcock YJ, Bedi M, Salerno KE, Severin D, Godette KD, Larrier NA, Curran WJ Jr, Torres-Saavedra PA, Lucas DR. Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials. JAMA Oncol. 2023 May 1;9(5):646-655. doi: 10.1001/jamaoncol.2023.0042.

Reference Type: DERIVED

PMID: 36995690 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25667281 (View on PubMed)

Other Identifiers

CDR0000582196

Identifier Type: -

Identifier Source: secondary_id

RTOG-0630

Identifier Type: -

Identifier Source: org_study_id