Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma

Sarcoma Clinical Trial

— STRASS  

Official title:

A Phase III Randomized Study of Preoperative Radiotherapy Plus Surgery Versus Surgery Alone for Patients With Retroperitoneal Sarcoma (RPS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01344018
• Other study ID #: EORTC-62092-22092
• Secondary ID: EORTC-62092EORTC
• Status: Completed
• Phase: N/A
• Start date: January 2012
• Est. completion date: March 2019

Study information

• Verified date: April 2023
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma

Intervention

Procedure:
• therapeutic conventional surgery

Radiation:
• 3-dimensional conformal radiation therapy

Locations

Country	Name	City	State
Belgium	Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet (101)	Brussels
Belgium	U.Z. Gasthuisberg	Leuven
Canada	CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame	Montreal QUEBEC	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Denmark	University Copenhagen	Herlev
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon
France	Institut Gustave Roussy	Villejuif
Germany	Universitaetsklinikum	Koeln
Germany	UniversitaetsMedizin Mannheim	Mannheim
Germany	Klinikum der Universitaet	Muenchen
Germany	Technische Universitaet Muenchen	Muenchen
Italy	Centro Di Riferimento Oncologico	Aviano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Clinico Humanitas	Milano
Italy	Istituto Oncologico Veneto	Padova
Netherlands	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
Norway	Radium Hospitalet	Oslo
Poland	Maria Sklodowska-Curie Memorial Cancer Center	Warsaw
Spain	Hospital General Vall d'Hebron	Barcelona
Spain	Hospital Universitario San Carlos	Madrid
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	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	Royal Marsden Hospital - Chelsea, London	London
United Kingdom	University College Hospital	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 States	Dana-Farber Cancer Institute & Harvard Medical School	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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	From date of randomization to the date of surgical procedure, prior to surgery
Secondary	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.	From the date of surgery, up to 60 days following surgery
Secondary	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.	From day 60 after surgery till end of follow-up, up to 7 years
Secondary	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.	Two weeks after completion of Pre-operative Radiotherapy, before Surgery
Secondary	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.	ARFI was measured from the date of randomization to the date of abdominal relapse, up to a maximum of 7 years
Secondary	Number of Patients With Metastases or Death	Alive and metastases free patients will be censored at the date of last follow-up.	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.
Secondary	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.	Overall survival was measured from the date of randomization to the date of death, whatever the cause, up to a maximum of 7 years