Surgery With or Without Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Retroperitoneum or Pelvis

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Giving radiation therapy before surgery may shrink the tumor so that it can be removed. It is not yet known whether surgery is more effective with or without radiation therapy. PURPOSE: This randomized phase III trial is studying surgery alone to see how well it works compared to radiation therapy together with surgery in treating patients with primary soft tissue sarcoma of the retroperitoneum or pelvis.

Detailed Description
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OBJECTIVES: Primary Compare progression-free survival of patients with primary soft tissue sarcoma of the retroperitoneum or pelvis treated with surgery with vs without preoperative radiotherapy. Secondary Compare the toxicity and complications associated with these regimens in these patients. Compare the rate of microscopically complete surgical resection in patients treated with these regimens. Compare the overall survival rate of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor grade (low [G1] vs intermediate [G2] vs high [G3/4]), tumor size (< 15 cm vs ≥ 15 cm), and tumor histology (liposarcoma vs non-liposarcoma). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo surgery. Arm II: Patients undergo preoperative radiotherapy once daily, 5 days a week, for 5.5 weeks. Within 28-63 days after the completion of radiotherapy, patients undergo surgery. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 28 days, 4 months, every 6 months for 5 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 370 patients (185 per treatment arm) will be accrued for this study within 4.5 years.

Official Title
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A Phase III Randomized Study of Preoperative Radiation Plus Surgery Versus Surgery Alone for Patients With Retroperitoneal Sarcomas (RPS)

Conditions
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Sarcoma

Intervention / Treatment
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* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary soft tissue sarcoma of the retroperitoneum or pelvis (e.g., iliac fossa) The following histologies are eligible: Alveolar soft part sarcoma Anaplastic sarcoma Angiosarcoma Atypical lipomatous tumor (low-grade liposarcoma) Clear cell sarcoma Epithelioid sarcoma Fibrosarcoma Leiomyosarcoma Liposarcoma (all subtypes) Malignant fibrous histiocytoma Malignant peripheral nerve sheath tumor Myxofibrosarcoma Neurofibrosarcoma Spindle cell sarcoma Synovial sarcoma Unclassified sarcoma The following histologies are not eligible: Rhabdomyosarcoma Extraosseous Ewing's sarcoma Primitive neuroectodermal tumor Osteosarcoma Chondrosarcoma Aggressive fibromatosis (desmoid tumor) Gastrointestinal stromal tumor Sarcomatoid carcinoma Hemangiopericytoma Retroperitoneal sarcomas located predominantly in the retroperitoneum extending across the inguinal ligament into the abdominal wall are allowed provided that ≥ 90% of the tumor volume is located within the retroperitoneal space No bowel obstruction OR history of previous bowel obstruction attributed to retroperitoneal tumor Primary non-visceral retroperitoneal masses consistent with sarcoma allowed provided diagnoses of carcinoma, melanoma, and lymphoma are excluded by immunohistochemistry Measurable gross disease by abdominopelvic CT scan (with IV and oral contrast) or MRI (with IV contrast) Patients must have undergone radiotherapy consultation within the past 30 days to confirm the feasibility of preoperative external-beam radiotherapy Patients must have undergone surgical consultation within the past 30 days to confirm and document the feasibility of macroscopically complete resection No prior macroscopically incomplete (R2) resection (i.e., partial debulking or subtotal tumor resection with gross residual disease) No pelvic sarcoma extending through the sciatic notch No clinical or radiographic evidence of probable metastatic disease Equivocal pulmonary or liver lesion allowed provided the likelihood of metastatic disease is small No sarcoma arising from bone or any retroperitoneal viscus (except the kidney) No sarcoma extending across the diaphragm into the thorax No recurrent retroperitoneal tumor No multifocal disease PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 OR Zubrod 0-1 Life expectancy Not specified Hematopoietic WBC ≥ 2,500/mm^3 Platelet count ≥ 80,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 2.5 times ULN Albumin normal* NOTE: *Higher levels allowed Renal Creatinine normal BUN normal Functional kidney confirmed by intravenous pyelogram and/or differential renal isotope scan Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation No other malignancy within the past 5 years (except effectively treated basal cell or squamous cell skin cancer) unless patient was curatively treated AND is at low risk for recurrence PRIOR CONCURRENT THERAPY: Chemotherapy No concurrent chemotherapy for primary tumor Radiotherapy No prior abdominal or pelvic irradiation No concurrent intraoperative or postoperative radiotherapy for primary tumor Surgery See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: surgery<br>Patients undergo surgery. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 28 days, 4 months, every 6 months for 5 years, and then annually for 5 years. | Procedure: conventional surgery<br> <br> |
| Experimental: radiation + surgery<br>Patients undergo preoperative radiotherapy once daily, 5 days a week, for 5.5 weeks. Within 28-63 days after the completion of radiotherapy, patients undergo surgery. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 28 days, 4 months, every 6 months for 5 years, and then annually for 5 years. | Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 5 years |  | at 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult alveolar soft-part sarcoma, adult angiosarcoma, adult epithelioid sarcoma, adult fibrosarcoma, adult leiomyosarcoma, adult liposarcoma, adult neurofibrosarcoma, adult synovial sarcoma, adult malignant fibrous histiocytoma, stage I adult soft tissue sarcoma, stage II adult soft tissue sarcoma, stage III adult soft tissue sarcoma