SarcomaSTRASSNCT01344018
Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma
A study testing therapeutic conventional surgery and 3-dimensional conformal radiation therapy in people with Sarcoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 37 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Sarcoma
- What is being tested?
- therapeutic conventional surgery and 3-dimensional conformal radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 266 participants
- Where
- 37 sitesin 13 countries
- Study dates
- Jan 2012to Mar 2019
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
37 sites in 13 countries.
37 sites in 13 countries
United Kingdom11 sites
Queen Elizabeth Medical Center
Birmingham, B15 2TH
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
Bristol
General Western Hospital
Edinburgh, EH4 2XU
Beatson-Gartnavel General Hospital
Glasgow, G12 0YN
Leeds Teaching Hospitals NHS Trust - St. James'S University Hospital
Leeds
University College Hospital
London, NW1 2PG
Royal Marsden Hospital - Chelsea, London
London
Christie NHS Foundation Trust
Manchester
Freeman Hospital
Newcastle, NE7 7DN
Nottingham University Hospitals NHS Trust - City Hospital campus
Nottingham
Weston Park Hospital
Sheffield, S10 2SJ
Germany4 sites
Universitaetsklinikum
Cologne, 50937
UniversitaetsMedizin Mannheim
Mannheim
Klinikum der Universitaet
München, 81377
Technische Universitaet Muenchen
München
Italy4 sites
Centro Di Riferimento Oncologico
Aviano, 33081
Istituto Clinico Humanitas
Milan, 20089
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
Istituto Oncologico Veneto
Padova, 35128
Netherlands4 sites
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
Amsterdam
University Medical Center Groningen
Groningen
Leiden University Medical Centre
Leiden, 2300
Radboud University Medical Center
Nijmegen, 6500
France3 sites
Institut Bergonie
Bordeaux, 33076
Centre Leon Berard
Lyon
Institut Gustave Roussy
Villejuif, 94805
Belgium2 sites
Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet (101)
Brussels, 1000
U.Z. Gasthuisberg
Leuven, 3000
Canada2 sites
CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame
Montreal Quebec, Quebec, 1560
Mount Sinai Hospital
Toronto, Ontario
Spain2 sites
Hospital General Vall d'Hebron
Barcelona, 08035
Hospital Universitario San Carlos
Madrid, 28040
United States1 site
Dana-Farber Cancer Institute & Harvard Medical School
Boston, Massachusetts, 02115
About this study
Official title: A Phase III Randomized Study of Preoperative Radiotherapy Plus Surgery Versus Surgery Alone for Patients With Retroperitoneal Sarcoma (RPS)
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.
Read the 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.
- Conditions
- Sarcoma
- Being tested
- therapeutic conventional surgery, 3-dimensional conformal radiation therapy
- 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
- Medical subject headings
- Sarcoma, Hemangiosarcoma, Fibrosarcoma, Leiomyosarcoma, Liposarcoma, Histiocytoma, Malignant Fibrous, Malignant mesenchymal tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic conventional surgeryProcedure or surgery
3-dimensional conformal radiation therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Surgery alone | Active comparator | En-bloc resection of surrounding tissues and organs when located within 1 to 2 cm from the surface tumor, even when not infiltrated. Receives: Procedure: therapeutic conventional surgery |
| Preoperative radiotherapy followed by en-bloc surgery | Experimental | 3D-CRT or IMRT to a dose of 50.4 Gy/28 daily fractions Receives: Procedure: therapeutic conventional surgery; Radiation: 3-dimensional conformal radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Abdominal Recurrence or Death
Abdominal recurrence was defined by one of the following events: local/abdominal or distant progressive disease during preoperative radiotherapy (as per RECIST 1.1), tumor or patient becoming inoperable (ASA score of 3 or involvement of superior mesenteric artery, aorta, or bone), peritoneal metastasis found at surgery, macroscopic residual disease left in at surgery (R2 resection), or local relapse (after macroscopically complete resection). Liver metastases were regarded as distant metastatic events. Patients with distant metastases were followed until local failure was detected. Patients without one of these events were censored at the date of last follow-up.
Measured: 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 (7)
Acute Toxicity Profile of Preoperative Radiotherapy.
The acute toxicity was assessed in randomized patients who received at least one dose of preoperative radiotherapy (RT). It follows Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 in the RT safety population, assuming the following classification:
- Grade 0 No event reported
- Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
- Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.
- Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
- Grade 4 Life-threatening consequences; urgent intervention indicated.
- Grade 5 Death related to AE. For each item of the CTCAE, the worst grade of acute toxicity from the data of randomization prior to surgery was taken
Measured: From date of randomization to the date of surgical procedure, prior to surgery
Perioperative Complications
Adverse events and side effects possibly related to surgery were assessed according to the Dindo's classification. This scales the observed side effects as Grade 0 No event Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions Grade II Requiring pharmacological treatment with drugs other than such allowed for grade I complications.
Grade III Requiring surgical, endoscopic or radiological intervention Grade IV Life-threatening complication (including CNS complications) requiring IC/ICU-management Grade V Death of a patient For each item, the frequency of the worst grade of the observed toxicity was tabulated by treatment group.
The perioperative period commence at the time of surgery (at the time of the induction anaesthesia) to the complete closure of the wound.
Measured: From the date of surgery, up to 60 days following surgery
Late Complications
The late toxicities occurring more than 60 days after surgery. These were reported using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. This scales the observed toxicity from Grade 1 to 5, assuming the following classification:
- Grade 0 no event
- Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
- Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.
- Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
- Grade 4 Life-threatening consequences; urgent intervention indicated.
- Grade 5 Death related to AE. Full AE reporting can be found in the Adverse Event Section.
Measured: From day 60 after surgery till end of follow-up, up to 7 years
Tumor Response to Preoperative Radiotherapy
For patients that received preoperative radiotherapy, the tumor response was assessed using RECIST 1.1. Response criteria were essentially based on a set of measurable lesions identified at baseline as target lesions, and followed at the end of the radiotherapy. Response was not the primary endpoint, so a confirmatory CT-scan was not mandatory.
Measured: Two weeks after completion of Pre-operative Radiotherapy, before Surgery
Number of Patients With an Abdominal Recurrence
Abdominal recurrence was defined in the ARFS section. The following are considered competing events:
- death in the absence of abdominal failure
- distant metastases diagnosed before abdominal failure Patients without one of these events were censored at the date of last follow-up.
Measured: ARFI was measured from the date of randomization to the date of abdominal relapse, up to a maximum of 7 years
Number of Patients With Metastases or Death
Alive and metastases free patients will be censored at the date of last follow-up.
Measured: 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.
Number of Patients Alive
Alive patients were censored at the date of last follow-up. Causes of death were recorded and reported as a table.
Measured: Overall survival was measured from the date of randomization to the date of death, whatever the cause, up to a maximum of 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2011 (estimated)
- Study startJan 2012
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SarcomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 266 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Sylvie Bonvalot, Study chair, Gustave Roussy, Cancer Campus, Grand ParisRick LM Haas, MD, Study chair, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01344018
- Sponsor's protocol ID
- EORTC-62092-22092
- Other IDs
- EORTC-62092, EORTC-22092, EU-21113
- Acronym
- STRASS
- Status last verified
- Apr 2023
- First submitted
- 27 Apr 2011
- Last updated
- 24 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 32941794