Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma

NCT ID: NCT01344018

Last Updated: 2023-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 266 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2019-03-31

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.

Conditions

Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Surgery alone

En-bloc resection of surrounding tissues and organs when located within 1 to 2 cm from the surface tumor, even when not infiltrated.

Group Type: ACTIVE_COMPARATOR

therapeutic conventional surgery

Intervention Type: PROCEDURE

Preoperative radiotherapy followed by en-bloc surgery

3D-CRT or IMRT to a dose of 50.4 Gy/28 daily fractions

Group Type: EXPERIMENTAL

therapeutic conventional surgery

Intervention Type: PROCEDURE

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

Interventions

therapeutic conventional surgery

Intervention Type: PROCEDURE

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sylvie Bonvalot

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus, Grand Paris

Rick LM Haas, MD

Role: STUDY_CHAIR

The Netherlands Cancer Institute

Locations

Dana-Farber Cancer Institute & Harvard Medical School

Boston, Massachusetts, United States

Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet (101)

Brussels, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Mount Sinai Hospital

Toronto, Ontario, Canada

CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame

Montreal Quebec, Quebec, Canada

University Copenhagen

Herlev, , Denmark

Institut Bergonie

Bordeaux, , France

Centre Leon Berard

Lyon, , France

Institut Gustave Roussy

Villejuif, , France

Universitaetsklinikum

Cologne, , Germany

UniversitaetsMedizin Mannheim

Mannheim, , Germany

Klinikum der Universitaet

München, , Germany

Technische Universitaet Muenchen

München, , Germany

Centro Di Riferimento Oncologico

Aviano, , Italy

Istituto Clinico Humanitas

Milan, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Istituto Oncologico Veneto

Padua, , Italy

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Leiden University Medical Centre

Leiden, , Netherlands

Radboud University Medical Center

Nijmegen, , Netherlands

Radium Hospitalet

Oslo, , Norway

Maria Sklodowska-Curie Memorial Cancer Center

Warsaw, , Poland

Hospital General Vall d'Hebron

Barcelona, , Spain

Hospital Universitario San Carlos

Madrid, , Spain

Karolinska University Hospital

Stockholm, , Sweden

Queen Elizabeth Medical Center

Birmingham, , United Kingdom

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre

Bristol, , United Kingdom

General Western Hospital

Edinburgh, , United Kingdom

Beatson-Gartnavel General Hospital

Glasgow, , United Kingdom

Leeds Teaching Hospitals NHS Trust - St. James'S University Hospital

Leeds, , United Kingdom

University College Hospital

London, , United Kingdom

Royal Marsden Hospital - Chelsea, London

London, , United Kingdom

Christie NHS Foundation Trust

Manchester, , United Kingdom

Freeman Hospital

Newcastle, , United Kingdom

Nottingham University Hospitals NHS Trust - City Hospital campus

Nottingham, , United Kingdom

Weston Park Hospital

Sheffield, , United Kingdom

Countries

United States; Belgium; Canada; Denmark; France; Germany; Italy; Netherlands; Norway; Poland; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 32941794 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

EORTC-62092

Identifier Type: OTHER

Identifier Source: secondary_id

EORTC-22092

Identifier Type: OTHER

Identifier Source: secondary_id

EU-21113

Identifier Type: OTHER

Identifier Source: secondary_id

EORTC-62092-22092

Identifier Type: -

Identifier Source: org_study_id