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

NCT00589121 | Completed Phase 2 Results DMC

• 2 other identifiers: RTOG-0630CDR0000582196
• Study Type: interventional
• Target: 98
• Locations: 2 countries
• Sites: 17

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Local Failure Rate at Two Years

  From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis.

• Regional Failure Rate at Two Years

  From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis.

• Distant Failure Rate at Two Years

  From registration to date of failure (distant progression) or death or last follow-up. Report at time of primary outcome measure analysis.

• Distant Disease-free Survival Rate at Two Years

  From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.

• Disease-free Survival Rate at Two Years

  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.

Other Outcomes (3)

• 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)

• 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)

• Comparison of SAQ Scores at 2 Years for Cohort A Patients With Cohort B Patients

  2 years after start of treatment (+/- 3 months)

Study Arms (2)

Cohort A - Chemotherapy

EXPERIMENTAL

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

Drug: Chemotherapy; Radiation: Radiation therapy; Procedure: Surgery

Cohort B - No Chemotherapy

EXPERIMENTAL

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

Radiation: Radiation therapy; Procedure: Surgery

Interventions

Chemotherapy DRUG

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

Cohort A - Chemotherapy

Radiation therapy 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.

Cohort A - Chemotherapy; Cohort B - No Chemotherapy

Surgery 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 A - Chemotherapy; Cohort B - No Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• NRG Oncology: collaborator

Study Sites (17)

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

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

Tampa, Florida, 33612-9497, United States

Location

Norton Suburban Hospital

Louisville, Kentucky, 40207, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, 48073, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

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

Hershey, Pennsylvania, 17033-0850, United States

Location

Norris Cotton Cancer Center - North

Saint Johnsbury, Vermont, 05819, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, T6G 1Z2, Canada

Location

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (2)

• 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.

  PMID: 36995690 DERIVED

• 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.

  PMID: 25667281 DERIVED

MeSH Terms

Conditions

Lymphedema; Radiation Fibrosis Syndrome; Radiation Injuries; Sarcoma; Chondrosarcoma, Extraskeletal Myxoid

Interventions

Drug Therapy; Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

Due to unmet accrual goals for Cohort A, the decision was made to close this cohort and to increase the sample size of Cohort B. Due to the small sample size for Cohort A results were not reported.

Results Point of Contact

• Title: Wendy Seiferheld, M.S.
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Dian Wang, MD, PhD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2008
• First Posted: January 9, 2008
• Study Start: March 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: May 21, 2018
• Last Updated: June 12, 2019
• Results First Posted: July 17, 2017

Record last verified: 2018-06

Locations

US (14); CA (3)