Clinical trial NCT00091351: Surgery With or Without Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Retroperitoneum or Pelvis
Official title: A Phase III Randomized Study of Preoperative Radiation Plus Surgery Versus Surgery Alone for Patients With Retroperitoneal Sarcomas (RPS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sarcoma
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-09-09
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival at 5 years
timeFrame: at 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Albany
country: United States
facility: Phoebe Cancer Center at Phoebe Putney Memorial Hospital
state: Georgia
city: Savannah
country: United States
facility: Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology Hematology Associates, Limited - West
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Olympia Fields
country: United States
facility: Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Portland
country: United States
facility: Cancer Institute at Oregon Health and Science University
state: Oregon
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Bethlehem
country: United States
facility: St. Luke's Hospital Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase-Temple Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Knoxville
country: United States
facility: U.T. Cancer Institute at University of Tennessee Medical Center
state: Tennessee
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
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: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Peter Pisters, MD
role: STUDY_CHAIR
References: