Clinical trial NCT01344018: Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma
Official title: A Phase III Randomized Study of Preoperative Radiotherapy Plus Surgery Versus Surgery Alone for Patients With Retroperitoneal Sarcoma (RPS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sarcoma
Keywords: adult angiosarcoma
adult fibrosarcoma
adult leiomyosarcoma
adult liposarcoma
adult malignant fibrous histiocytoma
adult malignant mesenchymoma
stage I adult soft tissue sarcoma
stage II adult soft tissue sarcoma
stage III adult soft tissue sarcoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2011-04-28
Enrollment: 266
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
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 kill tumor cells. Giving radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether surgery is more effective with or without radiation therapy in treating nonmetastatic retroperitoneal soft tissue sarcoma.

PURPOSE: This randomized phase III trial is studying radiation therapy followed by surgery to see how well it works compared with surgery alone in treating patients with previously untreated nonmetastatic retroperitoneal soft tissue sarcoma.

Detailed description: OBJECTIVES:

Primary

* To assess whether there is a difference in abdominal recurrence-free survival between retroperitoneal soft tissue sarcoma patients undergoing curative intent surgery alone and those undergoing preoperative radiotherapy followed by curative-intent surgery.

Secondary

* To assess whether there is a difference in metastasis-free survival, abdominal recurrence-free interval, and overall survival between these patients.
* To assess tumor response in patients undergoing preoperative radiotherapy.
* To assess toxicity of preoperative radiotherapy given prior to curative-intent surgery in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to institution and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo surgical resection of the tumor mass within 4 weeks following randomization.
* Arm II: Patients undergo 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT within 8 weeks after randomization. RT continues 5 days a week for approximately 5.5 weeks. Patients undergo surgical resection of the tumor mass within 4-8 weeks after the completion of RT.

Tumor tissue, normal abdominal wall fat, and peripheral blood may be collected during surgery to identify new prognostic factors for translational research.

After completion of study therapy, patients are followed at day 60 post-surgery and every 6 months thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed retroperitoneal sarcoma (RPS) by local pathologist, imaging-guided or surgical biopsy, including the following:

  * Primary soft tissue sarcoma of retroperitoneal space or infra-peritoneal spaces of pelvis
  * Sarcoma not originated from bone structure, abdominal, or gynecological viscera
  * Unifocal tumor (not multifocal disease)
  * Absence of extension through the sciatic notch or across the diaphragm
* The following histological sub-types are not allowed:

  * Gastrointestinal stromal tumor (GIST)
  * Rhabdomyosarcomas
  * Primitive neuroectodermal tumor (PNET) or other small round blue cells sarcoma
  * Osteosarcoma or chondrosarcoma
  * Aggressive fibromatosis
  * Sarcomatoid or metastatic carcinoma
* No metastatic disease
* Untreated disease
* Tumor must be operable and suitable for radiotherapy, based on the following criteria:

  * Pre-treatment CT scan/MRI and multidisciplinary consultation with surgeon, radiation oncologist, and radiologist (anticipated macroscopically complete resection, R0/R1 resection)

    * No surgery anticipated to be R2 on the CT scan before randomization
  * Must have American Society of Anesthesiologist (ASA) score ≤ 2
  * None of the following unresectable criteria:

    * Involvement of superior mesenteric artery
    * Involvement of aorta
    * Involvement of bone
* Must have radiologically measurable disease (RECIST 1.1), as confirmed by abdomino-pelvic CT (with IV and PO contrast) or MRI (with IV contrast)

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* WBC ≥ 2,500/mm\^3
* Platelet count ≥ 80,000/mm\^3
* Total bilirubin \< 1.5 times the upper limit normal
* Calculated creatinine clearance normal
* Functional contra-lateral kidney to the side involved by the RPS as assessed by intravenous pyelogram
* Adequate cardiac function (NYHA class I-II)
* ECG normal (without clinically significant abnormalities)
* No history of any of the following disorders:

  * Bowel obstruction
  * Mesenteric ischemia
  * Severe chronic inflammatory bowel disease
* Negative pregnancy test
* Not pregnant or nursing concurrently and for at least 1 month after the surgery
* Fertile patients must use effective contraception during the study treatment period and for at least 1 month after the surgery
* No co-existing malignancy within the past 5 years, except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
* No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

* No prior surgery (excluding diagnosis biopsy), radiotherapy, or systemic therapy
* No prior abdominal or pelvic irradiation for another prior malignancy or other disease
* No concurrent systemic anticancer treatment (chemotherapy, molecular-targeted therapy)
* No postoperative radiotherapy planned

Primary outcomes:
measure: Number of Patients With Abdominal Recurrence or Death
timeFrame: ARFS was measured from date of randomization to date of abdominal relapse or death, whichever occurred first, up to a maximum of 7 years.
Secondary outcomes:
measure: Acute Toxicity Profile of Preoperative Radiotherapy.
timeFrame: From date of randomization to the date of surgical procedure, prior to surgery
measure: Perioperative Complications
timeFrame: From the date of surgery, up to 60 days following surgery
measure: Late Complications
timeFrame: From day 60 after surgery till end of follow-up, up to 7 years
measure: Tumor Response to Preoperative Radiotherapy
timeFrame: Two weeks after completion of Pre-operative Radiotherapy, before Surgery
measure: Number of Patients With an Abdominal Recurrence
timeFrame: ARFI was measured from the date of randomization to the date of abdominal relapse, up to a maximum of 7 years
measure: Number of Patients With Metastases or Death
timeFrame: Metastases free survival was measured from the date of randomization to the date of occurrence of distant metastases or death, whichever occurred first, up to a maximum of 7 years.
measure: Number of Patients Alive
timeFrame: Overall survival was measured from the date of randomization to the date of death, whatever the cause, up to a maximum of 7 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute & Harvard Medical School
state: Massachusetts
city: Brussels
country: Belgium
facility: Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet (101)
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal QUEBEC
country: Canada
facility: CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame
state: Quebec
city: Herlev
country: Denmark
facility: University Copenhagen
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Koeln
country: Germany
facility: Universitaetsklinikum
city: Mannheim
country: Germany
facility: UniversitaetsMedizin Mannheim
city: Muenchen
country: Germany
facility: Klinikum der Universitaet
city: Muenchen
country: Germany
facility: Technische Universitaet Muenchen
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Oslo
country: Norway
facility: Radium Hospitalet
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center
city: Barcelona
country: Spain
facility: Hospital General Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Medical Center
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
city: Edinburgh
country: United Kingdom
facility: General Western Hospital
city: Glasgow
country: United Kingdom
facility: Beatson-Gartnavel General Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust - St. James'S University Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Chelsea, London
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital campus
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Sylvie Bonvalot
role: STUDY_CHAIR
affiliation: The Netherlands Cancer Institute
name: Rick LM Haas, MD
role: STUDY_CHAIR
References:
citation: Bonvalot S, Gronchi A, Le Pechoux C, Swallow CJ, Strauss D, Meeus P, van Coevorden F, Stoldt S, Stoeckle E, Rutkowski P, Rastrelli M, Raut CP, Hompes D, De Paoli A, Sangalli C, Honore C, Chung P, Miah A, Blay JY, Fiore M, Stelmes JJ, Dei Tos AP, Baldini EH, Litiere S, Marreaud S, Gelderblom H, Haas RL. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1366-1377. doi: 10.1016/S1470-2045(20)30446-0. Epub 2020 Sep 14.