High Versus Lower Intensity Surveillance Following Resection of Retroperitoneal Sarcoma (SARveillance)

An International, Partially-randomised, Patient-preference Trial Within a Registry of High Versus Lower Intensity Radiological Surveillance Following Primary Resection of Retroperitoneal, Abdominal and Pelvic Soft Tissue Sarcoma

The SARveillance trial is an efficient, pragmatic, multi-centre, international, stratified, partially-randomised, patient-preference trial within a registry of high versus lower intensity radiological surveillance following primary resection of retroperitoneal, abdominal and pelvic soft tissue sarcoma. The trial design is stratified by sarcoma tumour grade (high/intermediate grade and low grade).

Study Overview

• Status: Not yet recruiting
• Conditions: Sarcoma,Soft Tissue; Sarcoma Retroperitoneal
• Intervention / Treatment: Diagnostic test: High-intensity radiological surveillance; Diagnostic test: Lower-intensity radiological surveillance

Detailed Description

The SARveillance trial is an efficient, pragmatic, multi-centre, international, stratified, partially-randomised, patient-preference trial within a registry of high versus lower intensity radiological surveillance following primary resection of retroperitoneal, abdominal and pelvic soft tissue sarcoma. The trial design is stratified by sarcoma tumour grade (high/intermediate grade and low grade). Both high and lower intensity follow-up represent current practice in different centres across the trial delivery network, with variation at a centre and surgeon level. SARveillance is co-produced in deep collaboration with a patient advisory group. The delivery network is trans-continental including major sarcoma centres in Europe, Asia, and the Americas with central coordination from Istituto Nazionale Tumori, Milan, Italy and Birmingham Centre for Observational and Prospective Studies (BiCOPS) University of Birmingham, UK. For centres that would otherwise be precluded from participating in SARveillance due to institutional level data sharing restrictions, provision has been made for prearranged Individual Participant Data Meta-Analysis (IPDMA). The IPDMA essentially replicates the instruments and processes of SARveillance at a single site level and allows for the PI to provide data for meta-analysis at the close of SARveillance, rather than sharing real-time data with the SARveillance servers at the coordinating institutions. Adult patients undergoing primary resection for retroperitoneal, abdominal and pelvic sarcoma will be eligible for inclusion. The trial design is innovative and efficient, implemented as a trial within an international registry, and adopting concepts from the pragmatic REaCT trial design methodology. Patients that are willing to be randomised will be allocated in a 1:1 ratio to a high or lower intensity follow-up schedule. For patients that decline randomisation, the trial has patient preference arms to maximise insight into decision-making processes in the context of a rare disease and maximise participant recruitment. The primary outcome measure is quality of life, measured as emotional functioning (EF) up to 5 years after surgery, measured 3-monthly, using the questions relating to the EF domain of the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30). Secondary outcomes for the trial will be overall survival up to 5 years after surgery, the cancer worry scale (EORTC library), health utility calculated using EuroQol Group EQ-5D-5L and cost-effectiveness health utility, measured using EQ-5D-5L. The primary outcome measure for low grade tumours is health utility. Pre-planned sub-studies will be conducted including an economic analysis, and validation study for a prognostic risk model.

• Study Type: Interventional
• Enrollment (Estimated): 584
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marco Fiore, MD; Phone Number: 022390 2910; Email: marco.fiore@istitutotumori.mi.it
• Study Contact Backup: Name: Daniela Salvatore, PhD; Phone Number: 022390 2796; Email: daniela.salvatore@istitutotumori.mi.it

Study Locations

• Italy
  • Lombardia
    • Milan, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Contact: Marco Fiore, MD; Phone Number: 022390 2910; Email: marco.fiore@istitutotumori.mi.it
      • Contact: Daniella Salvatore, PhD; Phone Number: 022390 2796; Email: daniela.salvatore@istitutotumori.mi.it
      • Contact: Marco Fiore, MD
• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2GW
      • University Hospitals Birmingham NHS Foundation Trust
      • Contact: Samuel Ford, PhD; Phone Number: +44 121 3715880; Email: samuel.ford@uhb.nhs.uk
      • Contact: James Glasbey, PhD; Phone Number: +44 121 3715880; Email: j.glasbey@bham.ac.uk
      • Contact: Samuel Ford, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (greater than 18 years)
• Primary resection
• Histologically confirmed retroperitoneal, abdominal or pelvic soft tissue sarcoma
• R0/R1 resection
• Eligible whether or not the participant undergoes neoadjuvant treatment

Exclusion Criteria:

• Metastatic disease at time of randomisation
• Recurrent, metastatic or residual disease identified on baseline CT imaging (3-4 months post primary resection)
• Reoperation for recurrent soft tissue sarcoma
• Re-resection following previous inadequate surgery
• R2 resection
• Patients receiving adjuvant therapy that will delay, interrupt or render radiological surveillance unpredictable
• Uterine sarcomas, gastrointestinal stromal tumour (GIST), fibromatosis, epithelial tumours, multifocal disease, sarcomas of bony origin
• Patient declined to consent to data sharing with RESAR (unless in a centre contributing via pre-planned IPDMA)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-intensity radiological surveillance; High/intermediate grade histology: 3-4 monthly CT scan up to 2-years postoperatively, 6-monthly CT scan from 2-5 years postoperatively (schedule 1) Low grade histology: 6-monthly CT scan up to 2-years postoperatively, annual CT scan from 2-5 years postoperatively (schedule 2)	Diagnostic test: High-intensity radiological surveillance; The standard approach to surveillance imaging will be contrasted CT (IV and oral contrast) of the chest, abdomen and pelvis. All patients require radiological assessment of the chest, abdomen and pelvis at each surveillance round. Tolerance will be given in the protocol for selected patients where CT is not suitable to receive alternative imaging such as MRI or combination of MRI and CT. Uncontrasted CT imaging is permissible where renal toxicity or allergy from intravenous contrast is of concern. The use of plain radiography is not permitted as an alternative to CT imaging of the chest.
Active Comparator: Lower-intensity radiological surveillance; High intermediate grade histology: 6-monthly CT scan up to 2-years postoperatively, annual CT scan from 2-5 years postoperatively (schedule 2) Low grade histology: Annual CT scan up to 2-years postoperatively, 18 monthly CT scan from 2-5 years postoperatively (schedule 3)	Diagnostic test: Lower-intensity radiological surveillance; The standard approach to surveillance imaging will be contrasted CT (IV and oral contrast) of the chest, abdomen and pelvis. All patients require radiological assessment of the chest, abdomen and pelvis at each surveillance round. Tolerance will be given in the protocol for selected patients where CT is not suitable to receive alternative imaging such as MRI or combination of MRI and CT. Uncontrasted CT imaging is permissible where renal toxicity or allergy from intravenous contrast is of concern. The use of plain radiography is not permitted as an alternative to CT imaging of the chest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emotional Functioning	Quality of life, assessed using Emotional Functioning domain (items 21-24) of the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30). Each of the four items for this functional domain are scored between 1 and 4 (range: 3) to a total of 16 points, scaled to a total out of 100 using a validated formula from the EORTC scoring manual.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From time of primary surgery to death (all-cause mortality) or last follow up	5 years
Cancer worry scale	Cancer-worry, assessed using four specific items from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life item library. Each of the four items are scored between 1 and 4 (range: 3) to a total of 16 points, scaled to a total out of 100 using a validated formula from the EORTC scoring manual.	5 years
Health utility	EuroQol Group EQ-5D-5L. Each of the five items are scored between 1 and 5 (range: 4) to a total of 25 points, scaled to a weighted index between 0 and 1 using a validated formula from the EUROQOL scoring manual.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Defined as time from primary surgery to radiological evidence of disease recurrence as defined by the revised-RECIST criteria, by definition will be decreased in the high intensity follow-up group. This will be adopted as a process measure rather than an outcome measure.	5 years

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Collaborators: M.D. Anderson Cancer Center; Mayo Clinic; Royal Marsden NHS Foundation Trust; McGill University; KU Leuven; The Cleveland Clinic; Emory University; University of Southern California; Ohio State University; Ottawa Hospital Research Institute; Heidelberg University; University Hospital Birmingham NHS Foundation Trust; The Netherlands Cancer Institute; University of Birmingham; Peter MacCallum Cancer Centre, Australia; Campus Bio-Medico University; Royal Prince Alfred Hospital, Sydney, Australia; Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium; University Hospital Padova; Dana-Farber/Brigham and Women's Cancer Center
• Investigators: Principal Investigator: Samuel Ford, PhD, samuel.ford@uhb.nhs.uk

Publications and helpful links

General Publications

• Baia M, Ford SJ, Dumitra S, Sama L, Naumann DN, Spolverato G, Callegaro D. Follow-up of patients with retroperitoneal sarcoma. Eur J Surg Oncol. 2023 Jun;49(6):1125-1132. doi: 10.1016/j.ejso.2022.02.016. Epub 2022 Mar 4.

Helpful Links

• TARPSWG July 2020 - Trial development meeting
• RCSEd Pump Priming Grant funding

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): December 1, 2033
• Study Completion (Estimated): December 1, 2033

Study Registration Dates

• First Submitted: June 24, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): June 28, 2024

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Surgery; Quality of life; Cost-effectiveness; Radiology; Surveillance
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: INT201/16(05/23)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For international centres that would otherwise be precluded from participating in SARveillance, due to institutional level data sharing restrictions, provision has been made for prearranged Individual Participant Data Meta-Analysis (IPDMA). The IPDMA essentially replicates the instruments and processes of SARveillance at a single site level and allows for the PI to provide data for meta-analysis at the close of SARveillance. As the IPDMA derived data is supported by identical trial processes and materials, the subsequent data submitted for meta-analysis will be comparable in quality, safeguarding the statistical integrity of SARveillance during the meta-analysis. Centres within the trial delivery network that utilise the IPDMA process will be internal sponsors for SARveillance at the institutional level and are required to complete a pre-emptive agreement to share unidentified data with the trial network coordinating institutions for meta-analysis when SARveillance closes.
• IPD Sharing Time Frame: Upon locking the study database upon completion of last patient's follow-up.
• IPD Sharing Access Criteria: After approval by the central Trial Management group and completion of a study data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No